Research - The Happy Lungs Project

2025 RET Cancer Research Update

Irene Guijarro Munoz — Fri, 19 Dec 2025 16:07:30 +0000

Your investment in The Happy Lungs Project has resulted in very exciting advances over the past year. Check out the RET Research Update webinar recording and recaps of the research presentations.

In the 4th Annual End-of-Year RET Research Webinar, industry partners and leading researchers shared the latest insights into RET biology, treatment resistance, and emerging strategies aimed at improving outcomes for patients with RET-driven cancers.

We are deeply grateful to all of the presenters for sharing their insightful and compelling perspectives on RET-positive cancer research and future directions. We also thank our sponsors – Lilly, Ellipses, and Rigel – and the nearly 130 participants and members of the broader RET lung cancer community who joined us for the 2025 RET Research Update.

Your continued support of The Happy Lungs Project is helping drive meaningful research progress. We invite you to watch the webinar recording and read the recap below.

Research Presentations:

Rigel Pharmaceuticals:

Dr. Cynthia Villarimo from Rigel Pharmaceuticals, shared updates on Rigel’s RET research pipeline, highlighting pralsetinib (Gavreto) and ongoing efforts to improve outcomes for patients with RET fusion–positive cancers. Rigel is a fully integrated biopharmaceutical company with three FDA-approved therapies across hematology and oncology, including Gavreto, for RET fusion–positive metastatic non-small cell lung cancer (NSCLC) and RET positive thyroid cancer. Approval of pralsetinib was supported by results from the ARROW trial, which demonstrated durable responses across RET-positive solid tumors.

Dr. Villarimo shared Rigel’s ongoing research that focuses on overcoming resistance through combination strategies, evaluating intracranial efficacy, and exploring RET fusions in additional tumor types, including pancreatic and colorectal cancers. Dr. Villarimo also highlighted challenges in biomarker testing, including long turnaround times of 2 or 3 weeks. These delays may contribute to some patients receiving chemotherapy instead of targeted therapy.

To support timely access, Rigel offers patient assistance programs, copay support, and free drug supply coordination. More information is available at RigelOneCare.com.

Ellipses Pharma:

On behalf of Ellipses Pharma, Dr. Alex Drilon, Medical Oncologist at Memorial Sloan Kettering Cancer Center, presented an overview of the evolving treatment landscape for RET fusion–driven cancers, with a focus on lunbotinib (EP0031), a next-generation RET inhibitor currently in global clinical development by Ellipses Pharma.

For patients with RET fusion–positive NSCLC, first-line treatment typically involves selective RET inhibitors such as pralsetinib or selpercatinib, which provide durable benefit for many patients. However, once resistance develops, treatment options are limited and often shift to non-targeted chemotherapy. This unmet need has driven the development of newer RET inhibitors designed to extend benefit and overcome resistance.

Dr. Drilon emphasized that not all investigational RET inhibitors are truly next generation. Key differentiators include the activity against RET resistance mutations, particularly the RET G810, improved brain penetration, and clinical activity in patients previously treated with selective RET inhibitors

Dr. Drilon mentioned that while many RET inhibitors are in development globally, particularly in Asia, few demonstrate these features. Lunbotinib is currently the only next-generation RET inhibitor in active clinical development across Asia, Europe, and the United States, with more than 500 patients treated worldwide. Early-phase studies have shown:

Meaningful tumor responses in RET fusion–positive lung and thyroid cancers
Activity in the brain, an important consideration for RET-driven NSCLC
Clinical responses in patients who previously progressed on pralsetinib or selpercatinib
Activity against the challenging RET G810 resistance mutation

The objective response rates exceeded 40%, with disease control observed in over 80% of patients, and side effects were generally mild to moderate.

Beyond monotherapy, Dr. Drillon mentioned that lunbotinib is now being studied in combination with chemotherapy, both in patients new to RET inhibitors and in those previously treated. This approach is supported by the lessons learned from EGFR-positive lung cancer, where combining EGFR targeted therapy (osimertinib) with chemotherapy improves outcomes compared with targeted therapy alone.

Lilly:

Dr. Aimee Lin and Dr. Jennifer Wright from Lilly shared updates on the RET inhibitor selpercatinib, focusing on a major formulation change designed to improve patient experience. While selpercatinib continues to show strong clinical benefit across RET-driven cancers, Lilly recently transitioned the drug from capsules to smaller, easier-to-swallow tablets.

Approved by the FDA in April 2024, the tablet formulation offers fewer pills per dose, more flexible dosing, and improved usability, which is especially important for pediatric patients. Feedback from patients notes that the change makes daily treatment feel “less of a thing,” underscoring Lilly’s commitment to patient-centered innovation.

Troper Wojcicki Philanthropies:

Dr. Caitlin Nichols of Troper Wojcicki Philanthropies shared an update on the Lung Cancer Genetics Study, a national research effort created in partnership with 23andMe Research Institute and more than 20 lung cancer advocacy organizations, including The Happy Lungs Project.

The study’s goal is to better understand how genetics, environment, and lifestyle factors influence lung cancer risk, early detection, and treatment. Participants provide a saliva sample for genetic analysis and complete surveys about diagnosis, biomarker testing, treatments, exposures, and family history. De-identified data are securely shared with qualified researchers, with patients involved in reviewing research proposals to ensure studies reflect community priorities.

Dr. Nichols shared that 23andMe has transitioned to the 23andMe Research Institute, a nonprofit organization dedicated to advancing medical research.

The study is open to any U.S. adult who has ever been diagnosed with lung cancer, at no cost to participants. More than 1,300 people have already enrolled, with a goal of reaching 10,000 participants. Early data show strong representation of women and younger patients. Sixteen patients with RET lung cancer have joined the study, and about 400 participants reported they had a tumor biomarker.

Dr. Nichols noted that by growing this study, researchers hope to identify genetic risk factors, improve screening strategies, and ultimately support the development of more personalized treatments. Community participation and advocacy partnerships remain central to the study’s success. Those interested in learning more or enrolling can visit 23andMe.com/lung-cancer.

Dr. John Heymach, MD Anderson Cancer Center:

Dr. John Heymach, Professor and Chair of Thoracic Head and Neck Medical Oncology at MD Anderson Cancer Center, shared new research advances from his team that were made possible through funding from The Happy Lungs Project.

A central focus of Dr. Heymach’s work is the idea that not all RET fusions are the same. While RET-positive lung cancers are often treated as a single group, Dr. Heymach’s team showed that different RET fusions, such as KIF5B and CCDC6, can behave differently and respond differently to treatment. Using RET cell lines engineered in the lab to carry different RET fusions and mutations, the researchers found meaningful differences in drug sensitivity, even among patients treated with the same RET inhibitors.

These laboratory findings are supported by clinical data. Patients with CCDC6-RET fusions showed longer progression-free survival and overall survival compared with those with KIF5B-RET fusions. This suggests that fusion type may influence outcomes and could eventually help guide treatment decisions.

The team is also uncovering important differences in how RET fusions arise in different settings. For example, KIF5B-RET fusions are more common at initial diagnosis, while CCDC6-RET and other fusions are more often seen as resistance mechanisms in patients with EGFR-mutant lung cancer, pointing to distinct biological contexts.

Another major focus of the research is RET drug resistance. Using an innovative approach called Lentimutate developed by Dr. Ralf Kittler (UT Southwestern), the team can rapidly generate and study all possible resistance mutations in RET, rather than waiting for them to emerge in patients. This has revealed that resistance patterns differ not only by drug (such as selpercatinib vs. pralsetinib), but also by fusion partner. This knowledge has already helped guide switching between RET inhibitors when resistance develops.

Beyond mutations in RET itself, the researchers are exploring alternative resistance pathways, including signaling through EGFR, HER3, and MET. Preclinical studies suggest that combining RET inhibitors with newer therapies, such as EGFR/HER3–targeted antibody-drug conjugates, may help overcome resistance.

Looking ahead, Dr. Heymach’s team is identifying new cell-surface targets that appear in drug-resistant or drug-tolerant cancer cells. These discoveries are already being used to develop experimental CAR-T therapies and T-cell engagers, offering potential new strategies for patients whose cancers no longer respond to current RET inhibitors. The group is also exploring AI-driven “digital twin” models to better predict treatment response and accelerate clinical research.

During the Q&A, Dr. Heymach further explained how researchers are using a new tool called “digital twins” to help test new cancer treatments faster and more accurately. Traditional clinical trials, especially large randomized trials, are very expensive and can take many years to complete. Because of this, companies are sometimes hesitant to run them. A digital twin is a computer-generated model of a patient, which is created using large amounts of real patient data. It includes information such as tumor size and how the cancer typically changes over time. Researchers use artificial intelligence to predict how a patient would be expected to do on today’s standard treatment. The goal of this approach is to speed up drug development, identify promising treatments sooner, and help bring effective new therapies to patients more quickly.

Dr. Mihaela Aldea, Institut Gustave Roussy:

Dr. Mihaela Aldea, Medical Oncologist at Institut Gustave Roussy, presented emerging research focused on treatment strategies after progression on selective RET inhibitors in RET fusion–positive NSCLC. Her work builds on a global RET registry launched in 2021 (RET-MAP), which now includes data from more than 500 patients across 48 centers worldwide, enabling detailed study of resistance and new therapeutic opportunities.

Dr. Aldea pointed out that while selective RET inhibitors have transformed care for patients with RET fusions, progression eventually occurs for many patients. At that point, treatment options are limited, as RET-positive tumors tend to respond poorly to immunotherapy, highlighting the need for new targeted approaches.

Dr. Aldea’s research focuses on identifying cell-surface targets that could be exploited by antibody drug conjugates (ADCs) or bispecific antibodies. By analyzing tumor samples from 93 RET-positive patients across 12 European institutions her team evaluated expression of targets including MET, HER2, EGFR, HER3, and TROP2 using immunohistochemistry and gene-expression profiling.

The findings revealed that TROP2 is commonly expressed in RET-positive lung cancers, consistent with other lung adenocarcinomas. More notably, MET expression was significantly higher in RET-positive tumors compared with RET-negative ones, and MET levels often increased after progression on RET inhibitors. Importantly, multiple targets were frequently co-expressed, suggesting that dual-target or bispecific therapies may be effective.

Another key discovery involved angiogenesis, the process by which tumors form new blood vessels. RET-positive tumors showed a stronger angiogenic gene-expression signature and this signature appeared to be further enriched after resistance to RET inhibitors. Laboratory models confirmed that resistant cancer cells could form vessel-like networks, a phenomenon known as vasculogenic mimicry.

Building on these findings, Dr. Aldea’s team tested bevacizumab, an anti-angiogenic drug, in combination with chemotherapy in preclinical models. The combination disrupted vessel-like structures, reduced tumor cell migration, and increased cancer cell death. Retrospective clinical data also suggested a signal of benefit for bevacizumab plus chemotherapy, including in first line treatment, although patient numbers were small, and results require confirmation in prospective studies.

Dr. Aldea concluded that MET and TROP2 are promising targets for future ADC development in RET-positive lung cancer, particularly at progression. Anti-angiogenic strategies, either with bevacizumab or newer VEGF and immune-targeting combinations, may offer additional options, especially in regions where selective RET inhibitors are not yet widely available. She pointed out that further prospective trials will be essential to determine how best to integrate these approaches into clinical care.

Dr. David Carbone, The Ohio State University Cancer Center:

Dr. David Carbone, Professor and Director of the James Oncology Center at The Ohio State University, discussed strategies to improve outcomes for patients with RET fusion positive lung cancer beyond current RET targeted therapies. While selective RET inhibitors have significantly advanced care, Dr. Carbone emphasized that drug resistance remains inevitable, highlighting the need for complementary approaches.

Dr. Carbone shared the plans for the creation of a multi-institution RET research consortium, coordinated through MD Anderson, to accelerate progress through shared resources, patient samples, and collaborative projects. This model would allow researchers to test new strategies, such as locally ablative therapies, antibody-drug conjugates (ADCs), and bispecific antibodies, more efficiently across institutions.

Dr. Carbone also outlined ongoing research aimed at identifying novel cell-surface protein targets specific to RET-driven tumors and to drug-tolerant “persister” cells that survive after initial treatment. Using advanced cell-surface proteomic techniques, his team has already identified promising new targets in other fusion-driven cancers (ALK), with plans to extend this work to RET fusions.

Together, these efforts aim to move beyond incremental improvements in TKIs and toward next-generation therapies that could delay resistance, improve durability of response, and ultimately enhance long-term outcomes for patients with RET-positive lung cancer.

The post 2025 RET Cancer Research Update appeared first on The Happy Lungs Project.

The Role of Biomarker Testing in Early-Stage NSCLC: Why It’s Not Just for Advanced Disease

Irene Guijarro Munoz — Mon, 15 Dec 2025 14:43:24 +0000

Advances in biomarker science are reshaping how patients are diagnosed with and manage early-stage lung cancer. These insights can help connect patients with the treatments most likely to benefit them.

By Anthony Sireci, M.D., senior vice president of clinical biomarkers, laboratories and diagnostics at Eli Lilly and Company

Often, when people hear “biomarker testing” in relation to lung cancer, they associate it with advanced-stage disease. However, the treatment paradigm for non-small cell lung cancer (NSCLC) has evolved significantly in recent years and we see more therapies being introduced in the earliest stages of cancer, including in the neoadjuvant setting. Similar to how we think about biomarker testing in the advanced stages, comprehensive genomic profiling (CGP) is proving to be just as critical in early-stage NSCLC.

CGP is a thorough type of biomarker testing that looks for alterations in the DNA and sometimes RNA of a patient’s tumor cells in a single test to better understand the genomic drivers of their cancer. CGP in early-stage NSCLC can help inform targeted treatment options for patients in whom a potentially actionable genomic target is detected, similar to how it is used in later stage cancer, allowing for a better understanding of one’s cancer and an opportunity to receive care that is tailored to an individual’s unique cancer profile earlier in the treatment journey.

Why Testing in Early-Stage Matters

For patients with early-stage NSCLC, surgery is typically the first step in treatment. But as the treatment landscape continues to shift, people with NSCLC are no longer limited to surgery. Increasingly, alternative options are being used before surgery (neoadjuvant) or after surgery (adjuvant), and healthcare professionals can use CGP results to help guide treatment decisions with their patients as more targeted therapies become available in these early settings.

As the number of lung cancer diagnoses increasingly occur at earlier stages, the role of CGP continues to grow. Early genomic testing is important as the genomic drivers of the disease remain consistent from diagnosis throughout the course of their disease, so CGP results are available to inform every therapy decision, including if a patient progresses to metastatic disease. Early stage CGP can also rule out immunotherapy in certain biomarker-positive patients. Delaying testing can result in losing valuable time on ineffective treatments and interventions, and when it comes to cancer care, time is always of the essence.

What Patients Can Expect from CGP

Once someone is diagnosed with lung cancer, the next essential step is a conversation between the patient and their care team about available treatment options, and this conversation should include plans for CGP.

Here’s what someone might expect from CGP testing, at a high-level:

Often, the tumor sample, or biopsy, that was collected from a patient for diagnosis, can be used for CGP
The biopsy sample is sent to a specialized lab
DNA and/or RNA is extracted from the sample
The genetic material is sequenced to identify potentially actionable mutations or alterations
A detailed report is generated and shared with the treating physician to help guide treatment decisions

The Impact of CGP on Treatment Options

Targeted therapies have become increasingly available for early-stage lung cancer, thanks to years of research and innovation. However, these treatments are only a viable option if a patient’s biomarkers are identified. For example, certain genomic alterations may qualify a patient for a specific therapy after surgery, or for a pre-surgical treatment that can shrink the tumor and improve surgical outcomes.

Just a decade ago, targeted therapies for early-stage NSCLC were nonexistent. Today, we’re seeing a rapid shift toward earlier diagnosis and intervention, with more therapies being approved or studied for use in early-stage patients. Over the next few years, this trend will likely only accelerate, making CGP at diagnosis a vital first step in ensuring patients have access to the most effective treatment options available at diagnosis.

Encouraging Uptake and Awareness

Patients and care teams both play a role in making early CGP routine practice. To ensure biomarker testing becomes a standard part of lung cancer care, several elements must work together: streamlined workflows that integrate testing into the diagnosis process, education for both patients and healthcare providers, and open communication between the two to keep testing front of mind.

For patients, a cancer diagnosis can be overwhelming. Amid the whirlwind of emotions, it’s important to remain focused on treatment and feeling empowered to ask a healthcare provider about CGP. Once results are available, understanding how they inform treatment plans can help patients take an active role in their care.

For care teams, staying abreast of the latest advancements in biomarker testing and maintaining efficient workflows are essential. Providers play a key role in making CGP a routine part of the diagnostic process, ensuring results are available as early as possible to guide treatment decisions.

CGP isn’t just for advanced NSCLC, it’s for all stages of lung cancer. The earlier it’s done, the more time patients and HCPs have to understand which options could be most effective.

Guest Author Bio:

Anthony “Nino” Sireci, MD is the senior vice president of clinical biomarkers, laboratories and diagnostics at Eli Lilly and Company.

Dr. Sireci is a board-certified Clinical Pathologist and a practicing molecular pathologist. Prior to joining Lilly, he was an Assistant Professor of Pathology and Cell Biology at Columbia University and a medical director in the Laboratory of Personalized Genomic Medicine at Columbia Medical Center.

He is an active member of the Association for Molecular Pathology (AMP) where he serves on the organization’s Strategy Committee and was the former vice chair for new codes and pricing on the Economic Affairs Committee. He is also a member of the Pathology Coding Caucus in the College of American Pathologists (CAP) and the Molecular Pathology Advisory Group in the American Medical Association (AMA).

Dr. Sireci received a bachelor’s degree in chemistry from New York University, a medical degree from the Johns Hopkins University School of Medicine, and a master’s degree in Biostatistics from the Mailman School of Public Health at Columbia University. He completed his residency training in Clinical Pathology in the New York Presbyterian Hospital-Columbia, where he also served as chief resident.

View more blog posts by Nino.

Questions or need more information? Contact us at info@happylungsproject.org

Learn more about biomarker testing

The post The Role of Biomarker Testing in Early-Stage NSCLC: Why It’s Not Just for Advanced Disease appeared first on The Happy Lungs Project.

2025 RET Webinar: Meet Our Speakers

Irene Guijarro Munoz — Mon, 27 Oct 2025 13:07:33 +0000

The 2025 RET Research Update is just around the corner, and we are excited to introduce the amazing speakers joining us this year! Meet the experts who are helping move RET research and hope forward.

Dr. John Heymach

Professor and Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center.

Dr. John Heymach is Chair of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center, where he holds the David Bruton Endowed Chair in Cancer Research. He is a graduate of Harvard University and Stanford (MD/PhD), and he completed his training at Brigham and Women’s Hospital and the Dana-Farber/Mass General Brigham fellowship in Medical Oncology.

As a physician-scientist, Dr. Heymach’s research centers on therapeutic resistance, and biomarker development in lung cancer. His work has driven groundbreaking studies and new therapeutic strategies for oncogene driven cancers such as KRAS-mutant, HER2-mutant, and EGFR-mutant lung cancer. He is also a dedicated and compassionate clinician, and one of the country’s leading experts on RET-driven cancers. His laboratory continues to lead impactful research that is shaping the future of the RET cancer field.

He is a dedicated and caring clinician and one of the RET leaders in the country. Dr. Heymach’s team has been investigating the various RET fusions and their roles in driving resistance to RET inhibitors. His lab has established a comprehensive map of RET fusions and mutations associated with RET inhibitor resistance and has conducted functional studies to assess their differential responses to RET-targeted therapies. They have also identified new molecular targets in RET cancer cells that may serve as the basis for novel therapeutic strategies.

Dr. David Carbone

Professor and Director of the James Thoracic Oncology Center at the Ohio State University Medical Center

Dr. David Carbone is Professor of Internal Medicine and Director of the James Thoracic Oncology Center at The Ohio State University Medical Center, where he holds the Barbara J. Bonner Chair in Lung Research. He earned his MD and PhD in Molecular Biology and Genetics from Johns Hopkins University. After completing residency at Johns Hopkins Hospital and a fellowship at the NCI, Dr. Carbone joined Vanderbilt University, where he led the Thoracic/Head and Neck Cancer Program and served as PI of the Lung Cancer SPORE and SPECS consortia before being recruited to Ohio State in 2012.

Dr. David Carbone is internationally recognized for his leadership and contributions to the field of thoracic oncology. He has dedicated his career to advancing the understanding of lung cancer genetics, with a focus on identifying genetic alterations that drive lung cancer development and progression. Dr. Carbone was part of the pioneering group that identified EGFR as a critical target in lung cancer. This discovery led to the development of the first targeted therapies for EGFR lung cancer, revolutionizing treatment approaches.

His research includes developing new therapeutic strategies for resistant disease and exploring novel drug combinations. Dr. Carbone has also investigated immune-based therapies in thoracic malignancies and the mechanisms of tumor-associated immunosuppression. He leads several clinical trials, and he has a long-standing involvement with patient advocacy foundations.

With more than 300 peer-reviewed publications and continuous NIH/NCI funding, he has played a pivotal role in shaping translational research and clinical innovation in lung cancer.

Dr. Mihaela Aldea

Medical Oncologist and Associate Professor at Institut Gustave Roussy

Dr. Mihaela Aldea is a medical oncologist and associate professor at Gustave Roussy, one of Europe’s leading cancer centers. Dr. Aldea specializes in thoracic oncology and precision medicine, focusing on oncogene-driven cancers such as RET cancer and the study of cancer resistance mechanisms and the development of novel therapeutic strategies. At Gustave Roussy, Dr. Aldea leads clinical and translational research initiatives aimed at advancing personalized treatment approaches for patients with thoracic malignancies.

Dr. Aldea has contributed to numerous peer-reviewed publications and has been recognized with the 2024 Young Investigator Award by the International Association for the Study of Lung Cancer (IASLC).

Dr. Mihaela Aldea has made significant contributions to the understanding and treatment of RET lung cancer. Dr. Aldea led the international RET-MAP study, a multicenter, retrospective analysis that collected real-world data from patients with RET fusion-positive lung cancer. The study provided insights into the clinical and biological characteristics of these patients, highlighting the efficacy of RET inhibitors in improving survival outcomes. Through her research, Dr. Aldea continues to advance the field of thoracic oncology, improving outcomes for patients with RET lung cancer.

Our Pharma Partners

Also, for the first time, representatives from the three pharmaceutical companies most active in RET clinical research – Lilly, Rigel, and Ellipses – will come together to provide the latest updates and address key questions from our community.

We hope this webinar will be valuable for RET patients and the entire RET community, whose dedication and collaboration make events like this possible.

Lung Cancer Genetic Study

We’ll also present the first update on the Lung Cancer Genetics Study, a collaboration between the lung cancer community, Troper Wojcicki Philanthropies, and the 23andMe Research Institute.

Join Us

Thursday, December 11
12:30pm – 2:30pm CT

Questions or need more information? Contact us at info@happylungsproject.org

Learn more about RET Research

The post 2025 RET Webinar: Meet Our Speakers appeared first on The Happy Lungs Project.

Join the POISE study at Massachusetts General Hospital

Irene Guijarro Munoz — Thu, 23 Oct 2025 17:18:05 +0000

Join the study! Researchers have developed POISE, a short program combining palliative and survivorship care for patients with advanced lung cancer.

POISE (Patient-centered, Optimal Integration of Survivorship and Palliative Care) study at Massachusetts General Hospital for patients with advanced lung cancer receiving targeted therapy including RET cancer patients.

New targeted treatments have helped people with advanced lung cancer live longer and have fewer symptoms, but patients still face a long and unpredictable illness, often with needs for support that aren’t fully met. Many struggle with worries about the future, unclear information about their prognosis, and misunderstandings about whether their cancer can be cured. While early palliative care can help patients feel better, cope with their illness, and communicate with their doctors, past studies were done before modern targeted therapies, so it’s unclear how best to support patients who may live longer with advanced cancer. Survivorship care, which usually focuses on people who have finished early-stage cancer treatment, can also help by supporting long-term health, lifestyle changes, and emotional well-being. To meet these needs, researchers developed POISE (Patient-centred, Optimal Integration of Survivorship and palliative carE), a short program combining palliative and survivorship care for patients with advanced lung cancer receiving targeted therapy for tumors harboring EGFR, ALK, ROS1 or RET mutations. POISE is designed to help patients manage emotions, understand their illness, communicate with their care team, and take care of their long-term health. This study describes whether POISE is practical, helpful, and acceptable to patients compared with usual care.

POISE includes four sessions (60 minutes) with a trained palliative care clinician, either in person or by video, to help patients cope with their illness, understand their prognosis, set goals, and manage their long-term health. Participants will also complete short surveys about their feelings, quality of life, and health management. Half of the participants will receive POISE, and the other half will receive usual care from their oncology team. The study aims to see if POISE is helpful, easy to use, and acceptable to patients, and the results will help doctors improve supportive care for people living with advanced lung cancer.

Current trial status

Recruitment and enrolment for the RCT began on 21 November 2024. Any changes to the status of the trial will be updated on ClinicalTrials.gov (trial registration number: NCT04900935).

Other clinical trials

View other RET clinical trials.

Learn more about RET Research

The post Join the POISE study at Massachusetts General Hospital appeared first on The Happy Lungs Project.

RET Studies Presented at the IASLC 2025 World Conference on Lung Cancer

Irene Guijarro Munoz — Fri, 12 Sep 2025 19:37:09 +0000

The 2025 IASLC World Conference on Lung Cancer was held in Barcelona, Spain, from September 6–9, where some important studies on RET were presented.

P3.03.12

YAP-Driven Modulation of HER3-Mediated Adaptive Resistance to RET Inhibitors in RET-Altered Cancer

Tadaaki Yamada

This study investigates mechanisms of resistance to RET tyrosine kinase inhibitors (RET-TKIs) in RET-altered cancers, particularly lung and thyroid cancers harboring RET fusions or mutations.

This study showed that adaptive resistance to RET TKIs emerges via reactivation of ERK signaling mediated by HER3 activation following RET-TKI treatment. YAP, a key Hippo pathway effector, is translocated to the nucleus upon RET inhibition, driving HER3 gene expression and thus enabling ERK reactivation and resistance. Cell lines with high YAP expression display reduced sensitivity to RET-TKIs, whereas YAP knockdown suppresses proliferation, suggesting YAP as a potential biomarker for RET-TKI responsiveness.

Importantly, combining the pan-HER inhibitor afatinib with selpercatinib effectively suppresses ERK reactivation and cell proliferation in RET-TKI resistant, YAP-high cancer cells in vitro and in vivo. This combination therapy shows superior tumor control compared to single agents.

Clinical analysis of 23 RET-positive non-small cell lung cancer patients treated with selpercatinib indicates that low intratumoral cytoplasmic YAP expression correlates with longer progression-free and overall survival, supporting YAP’s role as a predictive biomarker.

In conclusion, YAP-driven HER3 activation constitutes a key adaptive resistance mechanism to RET-TKIs. Early combination therapy targeting both RET and HER3 pathways may overcome resistance, and assessing tumor YAP levels can guide treatment stratification for improved outcomes in RET-altered cancers.

P3.03.49

Mechanisms of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer Cells Harbouring RET Fusions

Eva Pros

In this study, researchers created RET-fusion lung cancer cells that became resistant to RET inhibitors using 2 RET cancer cell lines: LC-2 and PDC6. They found that in these cell lines, resistance arise mainly from the activation of other growth pathways (AKT, ERK, mTOR) or the development of new mutations in KRAS or NRAS genes. Some cells also developed a brand-new gene fusion that helped them survive.

These results show that RET-positive lung cancers often escape treatment by turning on backup pathways, meaning combination therapies will likely be needed to block resistance and improve outcomes.

P3.12.06

Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC

Domenico Galetta

This study compares the outcomes of pralsetinib, to best available therapy (BAT) (tyrosine kinase inhibitors (e.g., cabozantinib, vandetanib) and chemotherapy) in patients with previously treated, advanced RET fusion-positive lung cancer, using data from the Phase 1/2 ARROW trial and a real-world (RW) external control cohort.

Key findings:

Objective response rate (ORR) was significantly higher with pralsetinib (61.4%) than BAT (25.9%).
Median progression-free survival (PFS) was 16.8 months for pralsetinib versus 3.5 months for BAT.
Median overall survival (OS) was not reached in the pralsetinib group but was 9.1 months in the RW cohort, with 12-month survival rates of 74.6% versus 58.4%.

Limitations: The study had a small real-world comparison group and some differences between patient groups.

In conclusion, pralsetinib demonstrated superior efficacy over BAT as second-line or later therapy in RET fusion-positive NSCLC, with higher response rates, and significantly improved progression-free and overall survival, supporting its use in this population following prior treatment.

P3.12.36

Multicenter Retrospective Study of Selpercatinib Treatment for Advanced or Recurrent RET Fusion-Positive NSCLC in Japan

Yasuhiro Mihashi

This multicenter retrospective cohort study in Japan evaluated the effectiveness and safety of selpercatinib in 27 patients with advanced or recurrent RET fusion-positive lung cancer.

Key findings:

Overall objective response rate (ORR) of 78% (21/27 patients).
ORRs were 80% in the previously treated group and 76% in the treatment-naïve group.
Median progression-free survival (mPFS) was 23.5 months overall, with treatment-naïve patients showing a longer mPFS (23.5 months) compared to previously treated patients (13.3 months).
Median overall survival (mOS) was not reached, with 1-year OS rates around 88%.

Regarding safety, grade 3 liver enzyme elevation (ALT increase) occurred in 41% of patients, indicating a higher incidence of severe liver dysfunction compared to global clinical trials (LIBRETTO-001 and LIBRETTO-431). This suggests that Japanese patients may experience more pronounced hepatic adverse events from selpercatinib.

In summary, selpercatinib demonstrated high efficacy in Japanese patients with RET fusion-positive NSCLC regardless of prior treatment or PD-L1 status. However, increased liver toxicity highlights the need for careful monitoring in this population. These findings support selpercatinib as a valuable treatment option while emphasizing the importance of managing adverse events in real-world Japanese clinical settings.

P3.12.58

Initial Results From Phase 1/2 Study of the RET-Selective Inhibitor Vepafestinib in Patients With RET-Aberrant Solid Tumors

Kiyotaka Yoh

RET-altered cancers have limited treatment options beyond existing selective RET inhibitors. Vepafestinib (TAS0953/HM06), a new RET-selective inhibitor, is being tested in the ongoing phase 1/2 MARGARET trial (NCT04683250).

As of November 2024, 32 patients were treated in dose escalation and 14 in dose expansion. The maximum tolerated dose was determined to be 500 mg twice daily after dose-limiting toxicities at higher levels. The most common side effects were headache, nausea, and malaise, mostly mild to moderate.

Early signals of antitumor activity were observed: in dose escalation, partial responses were seen in both RET-inhibitor–naïve and pretreated patients with lung and thyroid cancers. In dose expansion, partial responses occurred in 2 of 4 treatment-naïve patients and 3 of 10 pretreated patients, with disease control rates of 50% and 80%, respectively.

Conclusion: Vepafestinib was generally well tolerated and showed promising early activity in both untreated and RET inhibitor–resistant patients, supporting further study.

P3.12.71

Efficacy and Safety of Pralsetinib in Patients With Advanced Ret Fusion-Positive NSCLC: Phase 1/2 ARROW Study Final Data

Aaron Mansfield

The phase 1/2 ARROW trial evaluated pralsetinib, a selective RET inhibitor, in patients with RET fusion–positive NSCLC. A total of 281 patients received pralsetinib 400 mg daily, with a median treatment duration of nearly 15 months.

Key findings:

Overall response rate (ORR): 70.3% (median duration of response 19.1 months)
Progression-free survival (PFS): 13.1 months
Overall survival (OS): 44.3 months with almost 4 years of follow-up
In the overall population, ORR, median DOR, and median PFS were higher in the US vs. Asia or Europe.
Responses were especially strong in patients <65 years (median duration of response 22.6 months)
Safety: 95% experienced treatment-related side effects, most commonly elevated liver enzymes, anemia, and hypertension; 66% had grade ≥3 events; 3 deaths were attributed to treatment-related causes. Importantly, no new safety concerns emerged.

Conclusion: Pralsetinib achieved durable, clinically meaningful responses in RET fusion lung cancer across treatment settings, with a manageable safety profile, confirming its role as a standard therapy option.

P3.18.63

Phase 1 Study of FHND5071, a Novel Selective RET Inhibitor, in RET Fusion-Positive Advanced NSCLC

Dechuang Yuan

FHND5071 is a new oral, selective RET inhibitor designed to achieve strong tumor and brain penetration, with preclinical studies showing up to 28× higher tumor exposure and 33× higher brain levels compared to selpercatinib. These properties support its potential for central nervous system (CNS) activity.

In the ongoing phase 1 trial (NCT05818917), 48 patients with advanced RET fusion–positive NSCLC were enrolled (29% with brain metastases; 77% previously treated). Patients received FHND5071 once daily (40–400 mg) in dose escalation or expansion cohorts. One patient did not receive treatment, leaving 47 in the ITT population.

Key findings:

Overall response rate (ORR): 68.1% (median duration of response not reached)
Progression-free survival (PFS): not reached
4 patients with measurable brain metastases. All of them achieved brain metastases shrinkage. The CNS Overall response rate (ORR) reached 100%.
Manageable safety profile

Conclusion: FHND5071 demonstrated robust activity in both systemic disease and brain metastases. Clinical outcomes and safety results are still being evaluated.

Learn more about RET Research

The post RET Studies Presented at the IASLC 2025 World Conference on Lung Cancer appeared first on The Happy Lungs Project.

Announcing the Lung Cancer Genetics Study Database

Irene Guijarro Munoz — Thu, 11 Sep 2025 15:06:57 +0000

Data initiative accelerates access to vital genetic and clinical insights.

We’re excited to announce the launch of the Lung Cancer Genetics Study Database! This database will allow qualified researchers to access de-identified data from consenting study participants at no cost. Research proposals will undergo a rigorous review process, and patients will help shape future research by reviewing and providing feedback on proposed research projects. To learn more and start the data access application process, contact study manager Caitlin Nichols at caitlin@twphilanthropies.org. To learn more about the Lung Cancer Genetics Study, visit www.23andme.com/lung-cancer #WCLC25. View the 23andMe blog post for more details.

At the 2025 World Conference on Lung Cancer in Barcelona, the 23andMe Research Institute, in collaboration with Troper Wojcicki Philanthropies and the health data software company Lifebit, introduced an open source platform that could help fast-track research discoveries through a powerful new cancer data repository.

The announcement comes just a year after the start of the Lung Cancer Genetics Study, spearheaded by 23andMe and bringing together more than 20 lung cancer advocacy and science organizations to recruit 10,000 people diagnosed with lung cancer. Their goal is to develop new ways to identify those at highest risk for lung cancer early, while also finding possible new treatments for this deadly cancer.

The post Announcing the Lung Cancer Genetics Study Database appeared first on The Happy Lungs Project.

Ellipses’ RET inhibitor EP0031 advances to Phase 2 clinical trials

Irene Guijarro Munoz — Thu, 10 Jul 2025 15:03:35 +0000

Ellipses’ next generation selective RET inhibitor EP0031 advances to Phase 2 clinical trials in the USA.

Clinical study for patients with RET+ solid tumors

EP0031 is a new specific RET inhibitor with broad activity against common RET fusions and mutations, including RET mutations that confer resistance to the RET inhibitors selpercatinib or pralsetinib and great brain penetration.

More info:

Infographic PDF

https://clinicaltrials.gov/study/NCT05443126

2025 ASCO RET highlights

Match to a clinical trial
Learn more about RET research

The post Ellipses’ RET inhibitor EP0031 advances to Phase 2 clinical trials appeared first on The Happy Lungs Project.

RET Highlights Presented at the 2025 American Society of Clinical Oncology (ASCO)

Irene Guijarro Munoz — Wed, 02 Jul 2025 18:56:30 +0000

The ASCO Annual Meeting 2025, held in Chicago, brought together oncology experts, researchers, and pharma leaders to discuss the latest advancements in clinical oncology.

Here are the RET lung cancer studies that were presented at the meeting this year.

Final results of a phase 1 study of EP0031, a next generation selective RET inhibitor (SRI) in patients with SRI naïve or pretreated advanced RET-altered tumors

Guzman Alonso. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

Ellipses’ next generation selective RET inhibitor EP0031 is a new specific RET inhibitor with broad activity against common RET fusions and mutations, including RET mutations that confer resistance to the RET inhibitors selpercatinib or pralsetinib and great brain penetration. It has been granted US Food and Drug Administration Orphan Drug and Fast Track Designation.

Final data from patients in the US and Europe was presented at the ASCO 2025 conference. In this study, a total of 40 patients were enrolled across dose cohorts (Most of them had lung cancer (NSCLC, 22 patients)), but over 400 patients have received EP0031 globally.

Among 40 treated patients, 32 were evaluable for response. 24 evaluable patients were previously treated with other RET inhibitors and 8 were naive patients (new to RET treatment).

Among patients previously treated with other RET inhibitors:

14 evaluable RET lung cancer patients: 5 patients had confirmed partial response and 5 had stable disease. Overall response rate was 42% and disease control rate was 83%.
7 evaluable RET thyroid cancer patients (MTC): 2 had partial response and 2 had stable disease. Duration of response was 6.5 – 9.6 months range.
3 evaluable other solid RET tumors the median duration of treatment was in the 1.7 – 3.9 months range.
2 non-evaluable patients due to having no measurable disease included a NSCLC patient who had stable disease for 16 weeks and a papillary thyroid carcinoma patient with stable disease for 36 weeks.

Among naive patients (new to RET treatment):

2 evaluable RET lung cancer patients: 1 had a complete response and 1 had a partial tumor response.
5 evaluable MTC patients: 4 patients had partial response and 1 patient had stable disease.

Brain lesions:

Among patients previously treated with other RET inhibitors, 3 of 4 evaluable patients with brain lesions had complete resolution of the lesions.
Among naive patients, 1 patient with brain lesions had complete resolution of the lesions

EP0031 demonstrated an acceptable safety and tolerability profile. Most treatment related side effects were manageable with temporary dose interruption (40% of the cases) and reductions (20%). Treatment related side effects leading to discontinuation was 2.5%.

Conclusions: EP0031-101 demonstrated promising safety and efficacy in a Phase 1 dose escalation and expansion trial, over long durations of treatment. It shows evidence of deep and durable responses in NSCLC regardless of exposure to prior treatment including selpercatinib and pralsetinib. Efficacy extends to patients with brain metastases, with complete resolution in several patients. It also demonstrates encouraging efficacy in other RET driven tumor types such as MTC. Phase 2 trials continue to evaluate EP0031 in the US, Europe, UAE and China.

View abstract

Rechallenge with first-generation RET inhibitors in RET-rearranged NSCLC pre-treated with selpercatinib or pralsetinib: Results from the RET MAP registry

Arianna Marinello. Cancer Medicine Department, Gustave Roussy

The RET MAP registry is an international, multicenter, retrospective study collecting genomic and clinical information from patients with NSCLC harboring a RET fusion who were diagnosed between February 2012 and April 2022. In this study, investigators examine the efficacy and safety of rechallenging RET NSCLC patients (continuing with the same RET inhibitor or switching the treatment to other same class RET inhibitor as single agent or in combination) who had previously progressed on selpercatinib or pralsetinib.

Out of 369 people who were treated with a first-generation RET inhibitor (selpercatinib or pralsetinib), about 38 people) were treated again with a drug from the same class later on, after their cancer progressed or they had to stop the original drug. The most common reason for stopping the first RET drug was cancer progression (71%). The rest stopped due to side effects (29%).

The same agent was maintained in 63% of the patients and in 27% of cases, doctors switched to a different first-generation RET drug. Most patients with progression received the RET drug alone (52%), while some had it combined with other targeted therapies (33%) or with chemotherapy (15%).

For patients who got a second RET drug alone after progression, the overall response rate was 18% and the median progression free survival was 2.14 months.
For those who got a second RET drug with other targeted treatments for bypass RET inhibitor resistance, the overall response rate was 38% and the median progression free survival was 4 months.
For patients who had to stop the first RET drug due to toxicity and were later given a different RET drug, the overall response rate was 50% and the median progression free survival was 9.89 months. But 3 out of 11 of these patients developed toxicity again.

Conclusions: Rechallenge a different RET inhibitor of the same class is effective after initial discontinuation due to toxicity, though recurrent toxicity may occur in one-third of patients. In contrast, RET inhibitor rechallenge after progression demonstrates limited efficacy, primarily in selected cases treated with combination therapies.

View abstract

First-in-human phase I/II study of BYS10 in patients (pts) with locally advanced or metastatic RET-altered solid tumors: Preliminary dose escalation results

Jie Wang, CAMS Key Laboratory of Translational Research on Lung Cancer, Cancer Hospital, Chinese Academy of Medical Sciences

BYS10 is a highly potent and RET-specific inhibitor that overcomes common RET resistant mutations (V804 and G810 mutations).

A total of 51 pts were enrolled in the study. In 40 evaluable patients, the confirmed overall response rate (ORR) and disease control rate (DCR) were 62.5% and 85% respectively. In the 30 evaluable patients with RET-fusion NSCLC, the overall response rate (ORR) and disease control rate (DCR) were 60% and 80 respectively. Intracranial antitumor activity was observed by investigators in 4 pts with at least 1 measurable intracranial lesion (one intracranial complete response).

Treatment related adverse events occurred in all subjects, the most common were: liver-related changes (high liver enzymes (AST in 64%, ALT in 58%) and high bilirubin (45%)), blood issues (low white blood cells (43%) and low neutrophils (33%)), and other lab changes (high uric acid (31%), low albumin (26%), and high creatinine (24%)). Other common symptoms included high blood pressure (29%) and headaches (24%). More serious side effects (moderate to severe, or grade 3 or 4) happened in some people, including: high AST (26%), high ALT (14%), High blood pressure (10%). Serious adverse events were recorded in 7 pts.

Conclusions: BYS10 showed preliminary antitumor activity in patients with RET-altered NSCLC. The study is still ongoing.

View abstract

Efficacy and safety of pralsetinib in patients with advanced RET-fusion-positive NSCLC: Final data from the phase 1/2 ARROW study.

Gilberto Lopes. Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine

Final results of the phase 1/2 ARROW (NCT03037385) study testing pralsetinib, a highly potent selective RET inhibitor for metastatic RET-altered NSCLC were presented.

281 patients with RET-fusion-positive NSCLC received pralsetinib with a median duration of treatment of 14.95 months. The overall response rate was 70% and median duration of response was 19.1 months. The median overall survival was 44.3 months. Median progression free survival was 13.1 months. The overall response rate and median progression free survival were markedly higher in the US (25.9 months, n=64) vs. Asia (12.6 months, n=122) or Europe (12.9 months, n=95).

Nearly all patients (95%) had some side effects from the treatment, and about two-thirds (66%) had more serious ones (moderate to severe). The most common side effects were:

High liver enzymes (AST in 46% and ALT in 35% of patients)
Anemia (low red blood cells) in 43%
High blood pressure in 27%

3 patients died from treatment-related complications:

2 from pneumonia
1 from lung inflammation (interstitial lung disease)
1 from severe muscle breakdown (rhabdomyolysis).

However, no new or unexpected safety issues were found in this update.

Conclusions: Pralsetinib produced clinically meaningful and durable responses in patients with RET-fusion-positive NSCLC (regardless of prior therapies) with a manageable safety profile, confirming with this longer follow up previously published results.

View abstract

Learn more about RET Research

The post RET Highlights Presented at the 2025 American Society of Clinical Oncology (ASCO) appeared first on The Happy Lungs Project.

RET Highlights Presented at the 2025 American Association for Cancer Research (AACR)

Irene Guijarro Munoz — Thu, 29 May 2025 13:55:10 +0000

The American Association for Cancer Research (AACR) Annual Meeting 2025, held in Chicago, highlighted a wide range of topics in cancer research, including groundbreaking clinical trials, cancer treatments, and latest innovations in cancer prevention.

Here are the RET studies that were presented at the AACR Annual Meeting this year.

5531/26 – A 3D CRISPR screening identified RET-TKI resistance through MIG6 loss in RET rearranged NSCLC

Xinzhao Wei et al. Japanese Foundation for Cancer Research, Koto City, Japan

To understand how certain cancer cells become resistant to RET-targeted treatments, scientists used a special 3D cancer cell culture system using RET cancer cell lines LC2/ad (CCDC6-RET) and LCC190 (CCDC6-RET) cell lines. They used a gene-editing technique (CRISPR) to turn off genes across the entire genome in the RET cell lines to identify genes that drive resistance to RET therapies and help cancer cells survive treatment.

One important gene they found was MIG6, which normally helps keep another cell pathway, EGFR, under control. When MIG6 was turned off, EGFR became overactive. This overactivity helped the cancer cells resist the RET-targeted treatment by turning on backup survival pathways in the cell.

These results show that when EGFR is not properly controlled, cancer cells can escape RET treatment. Combining RET-targeted drugs with EGFR inhibitors might be a promising therapeutic strategy to overcome drug resistance.

5611/21 – Preclinical evaluation of SNH-110: A potent, selective, next-generation RET inhibitor overcoming adaptive drug resistances

Shaomei Zeng, et al. ScinnoHub Pharmaceutical Co., Ltd., Chengdu, China, Chengdu Brilliant Pharmaceutical Co., Ltd., Chengdu, China

Despite the remarkable efficacy of pralsetinib and selpercatinib cancer cells can develop new mutations in the RET molecule, like G810C/S/R RET mutations, that make these treatments stop working. To tackle this problem, scientists have developed a new drug called SNH-110, which is a next-generation RET inhibitor. This new drug is especially effective against cancer cells that have these RET resistant G810 mutations.

SNH-110 has shown strong results in RET cell lines and in RET mouse models, shrinking tumors in cancers driven by RET alterations. Researchers plan to apply to the FDA in 2025 to begin testing SNH-110 in humans.

6382 – DNA damage repair pathways enable a drug-tolerant persister state in RET-fusion NSCLC and precedes TKI resistance

Fathema Z. Uddin, et al. Memorial Sloan Kettering Cancer Center, New York, NY.

To study how some RET lung cancers become resistant to RET-targeted treatments, researchers studied tumor samples from RET patients before and after they received RET inhibitors. They found that in resistant tumors, a gene called RB1 was turned off, and systems that repair DNA damage (called DNA damage repair or DDR pathways) were more active.

To test this in the lab, they turned off RB1 or increased the activity of a related protein called E2F in cancer cells, which caused important DNA repair genes—like BRCA1, MSH6, and Rad18—to become more active.

Then, they blocked these DDR pathways and found that doing so reduced the number of cancer cells that survived treatment (also known as drug-tolerant persister cells, which are the are cancer cells that survive treatment with targeted therapies and are seeds of resistant cells).

They also tested blocking a protein called XPO1, which is tied to the DDR process. When they combined an XPO1-blocking drug called selinexor (already FDA-approved) with the RET-targeted drug selpercatinib, it dramatically reduced the number of drug-tolerant persister cells.

They confirmed these results in mice using tumors grown from patient samples: the drug combo delayed the cancer from coming back and even helped re-sensitize previously resistant tumors to selpercatinib.

This research highlights DDR pathways as a critical mechanism of RET inhibitor resistance, and that blocking XPO1 might be a powerful way to overcome this resistance.

7211/17 – Proteolysis targeting chimeras (PROTACs) of oncogenic RET protein

Shriya Pandey, et al. University of Southern Florida, Tampa, FL.

To identify new more effective treatment options for RET cancer patients, scientists developed a new type of cancer drug called PROTAC (PROteolysis TArgeting Chimera) that binds the RET protein and help the machinery of the cell to destroy the protein altogether.

In this study, scientists created and tested several PROTACs designed to target the RET protein. A lead compound, YW-N-7, was selected based on in vitro and in vivo analyses.

Using the cancer cell line BaF3 KIF5B-RET fusion model, YW-N-7 was able to inhibit and degrade the KIF5B-RET fusion oncoprotein in RET mouse models, and significantly inhibited tumor growth. This work illustrates the potential of developing a RET PROTAC for simultaneously inhibiting and degrading oncogenic RET for cancer therapy.

Learn more about RET Research

The post RET Highlights Presented at the 2025 American Association for Cancer Research (AACR) appeared first on The Happy Lungs Project.

Cancer Cell Lines: Consider Donating to Advance Research

Irene Guijarro Munoz — Wed, 21 May 2025 17:20:23 +0000

Donating tumor tissue for research is a powerful way for patients to contribute to scientific progress and help others affected by RET-positive cancers.

Our ability to fully understand RET biology and drug resistance mechanisms continues to be hindered by the limited availability of well-characterized RET cancer cell models.

What are Cancer Cell Lines?

Cancer cell lines are cultures of cancer cells that can grow and divide indefinitely under controlled laboratory conditions. Cell lines are a cornerstone of cancer research, providing scientists with a reliable and reproducible way to study cancer cells in a controlled laboratory environment. They are essential tools in cancer research, allowing scientists to study tumor biology, test new therapies, and explore mechanisms of resistance.

These cell lines are typically derived from tumor samples collected from patients through biopsy or surgical resection. RET-positive cancer cell lines have most commonly been established from lung and thyroid cancers, where RET alterations occur more frequently.

Why Are RET Cancer Cell Lines Important for RET Research?

Compared to other oncogenic drivers such as EGFR or KRAS, there are very few RET fusion-positive cancer cell lines available worldwide. The limited availability of these cell lines hampers the study of genetic alterations and their role in RET cancer research. While existing models like LC-2/ad and TPC-1 are widely used, they represent only a limited portion of the RET fusion spectrum and patient diversity. Understanding drug sensitivity in these models is crucial for developing effective therapies.

RET fusions can involve a variety of partner genes – KIF5B-RET and CCDC6-RET being the most common – but other fusion variants have been identified in patients. Unfortunately, many of these fusion types lack representative cell lines, making it difficult to study them in the lab or develop novel treatments that could improve patient outcomes.

Expanding the collection of RET fusion-positive cancer cell lines is critical for advancing research in areas such as:

Understanding how resistance to RET inhibitors develops over time
Identifying combination therapies that may improve long-term outcomes
Investigating why some patients respond better to one RET inhibitor over another
Developing next-generation RET inhibitors or potential immunotherapy strategies

Gene expression data is also essential for understanding the biology of RET cancers and developing targeted therapies. Tumor cell lines play a pivotal role in research, providing continuous models that facilitate advancements in understanding cancer mechanisms and drug development.

How a RET Cancer Patient Can Donate Tissue for Cell Line Generation?

Donating tumor tissue for research is a powerful way for patients to contribute to scientific progress and help others affected by RET-positive cancers. Human cancer cell lines derived from donated tissue are crucial for studying cancer biology and developing new treatments. Here’s how the process typically works:

1. Talk to Your Medical Team

Ask your oncologist or surgeon if tissue from an upcoming biopsy or surgery can be used for research on human cancer cell lines, which are significant for studying cancer biology and treatment development. They can refer you to a research coordinator or a clinical trial team that works with tissue biobanks.
Many academic medical centers, NCI-designated cancer centers, and research hospitals have tissue banks and active cell line development programs, including advancements in gene therapy. If your care center does not, you can still ask them to coordinate with other labs that do (e.g., Dana-Farber, MD Anderson Cancer Center, Memorial Sloan Kettering, etc.).

2. Consent Is Required

You will be asked to sign a consent form allowing your tissue to be used for research, including the study of human cancer cell lines, which are significant for understanding cancer biology and developing treatments, and possibly shared with other institutions. This form will explain what will be done, how your privacy is protected, and your rights as a donor.
Your sample is typically de-identified (your name and details are removed).

Feeling overwhelmed? If you’re interested in donating tissue for a cell line, The Happy Lungs Project is here to help – just reach out, and we’ll help facilitate the process.

What Happens After Donation?

Once the tumor tissue is removed, either via biopsy or surgery, any portion not needed for diagnosis or treatment may be sent to a research lab. There, scientists attempt to grow the cancer cells under specialized conditions to develop a patient-derived cell line. These human cancer cell lines are significant in cancer research as they provide insights into oncogenic mechanisms and therapeutic targets.

It’s important to note that not all samples successfully grow, and success rates vary based on factors such as:

Tumor type
Tissue quality and size
Whether the patient has received prior treatment
The time and method of processing the tissue

Typically, success rates range from 10% to 30%, though this can vary. If successful, the resulting cell line becomes a renewable resource for laboratory studies that could benefit many future patients. Recent advancements in gene therapy, particularly with CRISPR technology, have shown promise in creating targeted gene knockouts to identify therapeutic targets.

Donating tissue for a cancer cell line can directly benefit the donor, as researchers are able to study the donor’s specific tumor, leading to more personalized insights and potentially advancing treatments tailored to cancer type.

From Cancer Cell Lines to Mouse Models

Xenograft models are also important as they allow researchers to study the behavior and characteristics of cancer cell lines in vivo, facilitating the examination of tumor development and metastasis. Mouse xenograft models are essential tools in cancer research, allowing scientists to implant human cancer cells or tissues into immunocompromised mice to study tumor biology, progression, and response to therapies in a controlled, living system. Mouse xenograft models involve transplanting human cancer cells into immunocompromised mice (often nude or NSG mice) to avoid immune rejection. The cells can be injected subcutaneously (under the skin) — the most common method or orthotopically (into the original tumor site, like lung) — for more realistic modeling.

RET Cancer Patients Make It Possible

The Happy Lungs Project has recently been reaching out to the RET-Positive cancer community through social media and private Facebook groups to request tissue donations for the development of RET cancer cell lines. Thanks to the incredible generosity of RET cancer patients, four new RET human cancer cell lines are now in development in the lab.

These potential new models are incredibly valuable, as they will enable researchers to study RET-driven cancers more closely, test new drugs, and explore novel therapeutic strategies. This work is a critical step toward accelerating the discovery of more effective and personalized treatments for RET patients.

We are deeply grateful to the RET cancer patients whose generosity made this possible.

References

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cancer-cell-line

Schubert L, Le AT, Estrada-Bernal A, Doak AE, Yoo M, Ferrara SE, Goodspeed A, Kinose F, Rix U, Tan AC, Doebele RC. Novel Human-Derived RET Fusion NSCLC Cell Lines Have Heterogeneous Responses to RET Inhibitors and Differential Regulation of Downstream Signaling. Mol Pharmacol. 2021 Jun;99(6):435-447. doi: 10.1124/molpharm.120.000207. Epub 2021 Apr 1. PMID: 33795352; PMCID: PMC11033948.

Hayashi T, Odintsov I, Smith RS, Ishizawa K, Liu AJW, Delasos L, Kurzatkowski C, Tai H, Gladstone E, Vojnic M, Kohsaka S, Suzawa K, Liu Z, Kunte S, Mattar MS, Khodos I, Davare MA, Drilon A, Cheng E, Stanchina E, Ladanyi M, Somwar R. RET inhibition in novel patient-derived models of RET-fusion positive lung adenocarcinoma reveals a role for MYC upregulation. Dis Model Mech. 2020 Dec 14;14(2):dmm047779. doi: 10.1242/dmm.047779. Epub ahead of print. PMID: 33318047; PMCID: PMC7888717.

Richter M, Piwocka O, Musielak M, Piotrowski I, Suchorska WM, Trzeciak T. From Donor to the Lab: A Fascinating Journey of Primary Cell Lines. Front Cell Dev Biol. 2021 Jul 22;9:711381. doi: 10.3389/fcell.2021.711381. PMID: 34395440; PMCID: PMC8356673.

The post Cancer Cell Lines: Consider Donating to Advance Research appeared first on The Happy Lungs Project.