{"id":4198,"date":"2025-05-29T09:55:10","date_gmt":"2025-05-29T13:55:10","guid":{"rendered":"https:\/\/happylungsproject.org\/?p=4198"},"modified":"2026-03-02T10:52:37","modified_gmt":"2026-03-02T15:52:37","slug":"ret-highlights-presented-at-the-2025-american-association-for-cancer-research-aacr","status":"publish","type":"post","link":"https:\/\/happylungsproject.org\/ret-highlights-presented-at-the-2025-american-association-for-cancer-research-aacr\/","title":{"rendered":"RET Highlights Presented at the 2025 American Association for Cancer Research (AACR)"},"content":{"rendered":"[vc_row type=”in_container” full_screen_row_position=”middle” column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” scene_position=”center” text_color=”dark” text_align=”left” row_border_radius=”none” row_border_radius_applies=”bg” overflow=”visible” overlay_strength=”0.3″ gradient_direction=”left_to_right” shape_divider_position=”bottom” bg_image_animation=”none” shape_type=””][vc_column column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” column_position=”default” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/1″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][vc_row_inner column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” text_align=”left” row_position=”default” row_position_tablet=”inherit” row_position_phone=”inherit” overflow=”visible” pointer_events=”all”][vc_column_inner column_padding=”padding-3-percent” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color=”#f68d28″ background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” font_color=”#ffffff” column_shadow=”none” column_border_radius=”10px” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/1″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid” column_padding_type=”default” gradient_type=”default”][vc_column_text css=”” text_direction=”default”]\n

The American Association for Cancer Research (AACR) Annual Meeting 2025, held in Chicago,\u00a0highlighted a wide range of topics in cancer research, including groundbreaking clinical trials, cancer treatments, and latest innovations in cancer prevention.\u00a0<\/span><\/p>\n[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][vc_row_inner column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” text_align=”left” row_position=”default” row_position_tablet=”inherit” row_position_phone=”inherit” overflow=”visible” pointer_events=”all”][vc_column_inner column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/1″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][vc_column_text css=”” text_direction=”default”]Here are the RET studies that were presented at the AACR Annual Meeting this year.<\/p>\n

 <\/p>\n

5531\/26 – A 3D CRISPR screening identified RET-TKI resistance through MIG6 loss in RET rearranged NSCLC<\/h2>\n

Xinzhao Wei et al. Japanese Foundation for Cancer Research, Koto City, Japan<\/i><\/p>\n

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<\/a> 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.<\/p>\n

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.<\/p>\n

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.<\/p>\n

 <\/p>\n

5611\/21 – Preclinical evaluation of SNH-110: A potent, selective, next-generation RET inhibitor overcoming adaptive drug resistances<\/h2>\n

Shaomei Zeng,\u00a0et al. ScinnoHub Pharmaceutical Co., Ltd., Chengdu, China, Chengdu Brilliant Pharmaceutical Co., Ltd., Chengdu, China<\/i><\/p>\n

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

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.<\/p>\n

 <\/p>\n

6382 – DNA damage repair pathways enable a drug-tolerant persister state in RET-fusion NSCLC and precedes TKI resistance<\/h2>\n

Fathema Z. Uddin,\u00a0et al. Memorial Sloan Kettering Cancer Center, New York, NY.<\/i><\/p>\n

To study how some RET lung cancers<\/a> 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<\/b> was turned off, and systems that repair DNA damage (called DNA damage repair or DDR pathways<\/b>) were more active.<\/p>\n

To test this in the lab, they turned off RB1 or increased the activity of a related protein called E2F <\/b>in cancer cells, which caused important DNA repair genes\u2014like BRCA1, MSH6, and Rad18<\/b>\u2014to become more active.<\/p>\n

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

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

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<\/b> to selpercatinib.<\/p>\n

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.<\/p>\n

 <\/p>\n

7211\/17 – Proteolysis targeting chimeras (PROTACs) of oncogenic RET protein<\/h2>\n

Shriya Pandey,\u00a0et al. University of Southern Florida, Tampa, FL.<\/i><\/p>\n

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

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.<\/p>\n

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.<\/p>\nLearn more about RET Research<\/span><\/a>[\/vc_column_text][vc_column_text css=”” text_direction=”default”][\/vc_column_text][\/vc_column_inner][\/vc_row_inner][vc_row_inner column_margin=”default” column_direction=”default” column_direction_tablet=”default” column_direction_phone=”default” text_align=”left” row_position=”default” row_position_tablet=”inherit” row_position_phone=”inherit” overflow=”visible” pointer_events=”all”][vc_column_inner column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/4″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][\/vc_column_inner][vc_column_inner column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/4″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][\/vc_column_inner][vc_column_inner column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/4″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][\/vc_column_inner][vc_column_inner column_padding=”no-extra-padding” column_padding_tablet=”inherit” column_padding_phone=”inherit” column_padding_position=”all” column_element_direction_desktop=”default” column_element_spacing=”default” desktop_text_alignment=”default” tablet_text_alignment=”default” phone_text_alignment=”default” background_color_opacity=”1″ background_hover_color_opacity=”1″ column_backdrop_filter=”none” column_shadow=”none” column_border_radius=”none” column_link_target=”_self” overflow=”visible” gradient_direction=”left_to_right” overlay_strength=”0.3″ width=”1\/4″ tablet_width_inherit=”default” animation_type=”default” bg_image_animation=”none” border_type=”simple” column_border_width=”none” column_border_style=”solid”][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row]\n","protected":false},"excerpt":{"rendered":"

RET Highlights Presented at the 2025 American Association for Cancer Research (AACR)<\/p>\n","protected":false},"author":15,"featured_media":4204,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[],"class_list":{"0":"post-4198","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-research"},"yoast_head":"\nRET Highlights - 2025 American Ass. for Cancer Research (AACR)<\/title>\n<meta name=\"description\" content=\"The American Association for Cancer Research (AACR) Annual Meeting 2025 featured groundbreaking clinical trials, cancer treatments, and latest innovations in cancer prevention.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/happylungsproject.org\/ret-highlights-presented-at-the-2025-american-association-for-cancer-research-aacr\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"RET Highlights - 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