{"id":650016,"date":"2026-08-22T02:06:03","date_gmt":"2026-08-22T02:06:03","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/650016\/"},"modified":"2026-08-22T02:06:03","modified_gmt":"2026-08-22T02:06:03","slug":"first-in-class-therapy-targets-undruggable-protein-in-hard-to-treat-blood-cancers","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/650016\/","title":{"rendered":"First-in-Class Therapy Targets \u201cUndruggable\u201d Protein in Hard-to-Treat Blood Cancers"},"content":{"rendered":"<ul>\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"1\" data-list-defn-props=\"{\" data-aria-posinset=\"1\" data-aria-level=\"1\">The\u00a0MYC\u00a0protein\u00a0is\u00a0involved\u00a0in about 70% of cancers, but scientists have\u00a0been unable\u00a0to develop drugs that\u00a0effectively block\u00a0it\u00a0<\/li>\n<\/ul>\n<ul>\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"1\" data-list-defn-props=\"{\" data-aria-posinset=\"2\" data-aria-level=\"1\">Researchers discovered a dependent relationship\u00a0in which\u00a0MYC and another protein\u00a0support each other in a reinforcing cycle\u00a0<\/li>\n<\/ul>\n<ul>\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"1\" data-list-defn-props=\"{\" data-aria-posinset=\"3\" data-aria-level=\"1\">A new\u00a0therapy\u00a0interrupts the cycle,\u00a0causing levels of both proteins to drop significantly\u00a0<\/li>\n<\/ul>\n<ul>\n<li aria-setsize=\"-1\" data-leveltext=\"\uf0b7\" data-font=\"Symbol\" data-listid=\"1\" data-list-defn-props=\"{\" data-aria-posinset=\"4\" data-aria-level=\"1\">Preclinical findings\u00a0demonstrated\u00a0strong anti-cancer activity in multiple types of blood cancers, including mutated and treatment-resistant models\u00a0<\/li>\n<\/ul>\n<p>Newswise \u2014 HOUSTON,\u00a0AUGUST\u00a021,\u00a02026\u00a0\u2015\u00a0A first-in-class therapy to\u00a0target MYC, one of the most sought-after and difficult targets in cancer biology,\u00a0showed\u00a0promise in hard-to-treat blood cancers, according to a new\u00a0preclinical\u00a0study from\u00a0<a href=\"https:\/\/www.mdanderson.org\/\" rel=\"nofollow noopener\" target=\"_blank\">The University of Texas MD Anderson Cancer Center<\/a>\u00a0published in\u00a0<a href=\"https:\/\/ashpublications.org\/blood\/article-abstract\/doi\/10.1182\/blood.2025030170\/570175\/Dual-MYC-and-GSPT1-Protein-Degrader-for-MYC-Driven\" rel=\"nofollow noopener\" target=\"_blank\">Blood<\/a>.\u00a0<\/p>\n<p>Researchers\u00a0led by\u00a0<a href=\"https:\/\/faculty.mdanderson.org\/profiles\/michael_andreeff.html\" rel=\"nofollow noopener\" target=\"_blank\">Michael Andreeff, M.D., Ph.D.<\/a>, professor, and\u00a0<a href=\"https:\/\/faculty.mdanderson.org\/profiles\/yuki_nishida.html\" rel=\"nofollow noopener\" target=\"_blank\">Yuki Nishida, M.D., Ph.D.<\/a>, assistant professor, both\u00a0of\u00a0<a href=\"https:\/\/www.mdanderson.org\/research\/departments-labs-institutes\/departments-divisions\/leukemia.html\" rel=\"nofollow noopener\" target=\"_blank\">Leukemia<\/a>, found\u00a0that experimental drug GT19630\u00a0interrupts\u00a0a\u00a0newly discovered\u00a0cycle\u00a0between MYC and GSPT1,\u00a0resulting in\u00a0strong anti-cancer activity in\u00a0preclinical models of\u00a0<a href=\"https:\/\/www.mdanderson.org\/cancer-types\/leukemia.html\" rel=\"nofollow noopener\" target=\"_blank\">leukemia<\/a>,\u00a0<a href=\"https:\/\/www.mdanderson.org\/cancer-types\/lymphoma.html\" rel=\"nofollow noopener\" target=\"_blank\">lymphoma<\/a>\u00a0and\u00a0<a href=\"https:\/\/www.mdanderson.org\/cancer-types\/multiple-myeloma.html\" rel=\"nofollow noopener\" target=\"_blank\">multiple myeloma<\/a>, including treatment-resistant and\u00a0TP53-mutated disease.\u00a0<\/p>\n<p>\u201cFor decades, scientists have\u00a0struggled to develop\u00a0therapies\u00a0that successfully\u00a0block\u00a0MYC,\u00a0leading many in the field to describe\u00a0it\u00a0as undruggable,\u201d Andreeff said. \u201cBy identifying a vulnerability in the relationship between MYC and GSPT1, we found a way to eliminate both proteins and\u00a0disable\u00a0a pathway many cancers depend on for survival.\u201d\u00a0<\/p>\n<p>How\u00a0does\u00a0this therapy successfully target MYC?<\/p>\n<p>One of the most important drivers of cancer growth,\u00a0the\u00a0MYC\u00a0protein\u00a0is involved in approximately 70% of all human cancers\u00a0and acts as a master switch,\u00a0regulating the genes that enable cancer cells to grow,\u00a0divide\u00a0and sustain their metabolism. While\u00a0blocking\u00a0this protein has been a high priority for cancer research,\u00a0scientists\u00a0have been unable to develop\u00a0a\u00a0therapy\u00a0that effectively\u00a0interferes with\u00a0MYC.\u00a0<\/p>\n<p>This study revealed a previously unknown relationship between MYC and GSPT1.\u00a0MYC helps activate the GSPT1\u00a0gene,\u00a0and\u00a0GSPT1 helps cancer cells produce MYC proteins, creating what researchers describe as a \u201cfeedforward loop\u201d that could be\u00a0exploited\u00a0therapeutically.\u00a0<\/p>\n<p>A new\u00a0protein degrader\u00a0drug called GT19630\u00a0disrupts\u00a0the cycle between MYC and GSPT1 by binding to both proteins and marking MYC for disposal using the cell\u2019s natural protein recycling system. The treatment simultaneously degrades GSPT1, causing levels of both proteins to drop significantly and\u00a0demonstrating\u00a0broader activity than targeting GSPT1 alone.\u00a0<\/p>\n<p>How\u00a0effective is this protein degrader against hard-to-treat blood\u00a0cancers?<\/p>\n<p>Preclinical models of leukemia,\u00a0lymphoma\u00a0and multiple myeloma were\u00a0highly sensitive\u00a0to GT19630.\u00a0Notably, the therapy\u00a0remained\u00a0effective in cells with\u00a0TP53\u00a0mutations,\u00a0which\u00a0often\u00a0are\u00a0associated with treatment resistance.\u00a0\u00a0<\/p>\n<p>GT19630 may\u00a0also\u00a0offer a path to overcome\u00a0venetoclax\u00a0resistance in\u00a0<a href=\"https:\/\/www.mdanderson.org\/cancer-types\/acute-myeloid-leukemia.html\" rel=\"nofollow noopener\" target=\"_blank\">acute myeloid leukemia (AML)<\/a>.\u00a0Researchers found that resistant AML cells had increased MYC and GSPT1 levels.\u00a0In preclinical models,\u00a0GT19630 restored sensitivity to venetoclax,\u00a0dramatically\u00a0prolonging\u00a0survival\u00a0\u2013\u00a0by\u00a0more than 300% in one model.\u00a0\u00a0<\/p>\n<p>Stem-like\u00a0AML cells, which\u00a0can survive treatment and contribute to relapse,\u00a0often\u00a0contain\u00a0higher levels of MYC than normal blood-forming\u00a0stem\u00a0cells.\u00a0Using single-cell RNA analysis,\u00a0researchers also\u00a0observed\u00a0elevated MYC levels in\u00a0TP53-mutant AML stem cells.\u00a0Their heightened dependence on\u00a0MYC\u00a0made the AML cells\u00a0more sensitive to\u00a0GT19630,\u00a0while\u00a0normal blood-forming\u00a0stem\u00a0cells were less\u00a0affected.\u00a0This suggests\u00a0a potential therapeutic window\u00a0in which the\u00a0drug\u00a0may selectively\u00a0impact\u00a0some of the most treatment-resistant leukemia cells while limiting damage to healthy bone marrow.\u00a0<\/p>\n<p>What\u2019s\u00a0next for this\u00a0approach?<\/p>\n<p>These findings\u00a0support\u00a0GT19630\u00a0as a potential\u00a0pathway to target MYC,\u00a0but\u00a0future studies are\u00a0needed to\u00a0determine\u00a0if this\u00a0strategy\u00a0is safe and effective in patients.\u00a0Cancers\u00a0with high\u00a0MYC activity may be especially vulnerable to this therapy, raising the possibility of using\u00a0<a href=\"https:\/\/www.mdanderson.org\/cancerwise\/how-are-biomarkers-used-in-cancer-treatment.h00-159855345.html\" rel=\"nofollow noopener\" target=\"_blank\">biomarkers<\/a>\u00a0to\u00a0identify\u00a0patients most likely to respond.\u00a0\u00a0<\/p>\n<p>The study\u2019s encouraging activity in venetoclax-resistant AML shows\u00a0significant translational promise,\u00a0and\u00a0further research\u00a0may evaluate GT19630 as a direct treatment\u00a0for resistant or relapsed AML or in combination with other\u00a0therapies.\u00a0\u00a0<\/p>\n<p>\u201cIn addition to\u00a0direct\u00a0MYC inhibition, this approach\u00a0harnesses the cell\u2019s own natural processes to eliminate it,\u201d Andreeff said. \u201cThis concept could help expand the use of protein degraders against\u00a0challenging\u00a0targets and inspire new therapeutic strategies\u00a0for\u00a0proteins once considered beyond the reach of conventional therapies.\u201d\u00a0<\/p>\n<p class=\"text-center\">***\u00a0<\/p>\n<p>This research was supported by\u00a0the\u00a0Paul and Mary Haas Chair in Genetics in Honor of Amanda Marie Whittle,\u00a0the\u00a0Cancer Prevention Research Institute of Texas (CPRIT), the National Institutes of\u00a0Health,\u00a0CURE\u00a0Childhood Cancer,\u00a0Children\u2019s Cancer Research Fund,\u00a0The\u00a0Robert A. Welch Distinguished Chair in Chemistry, and UT MD Anderson institutional funding.\u00a0A full list of collaborating authors and their disclosures can be found with the full paper in\u00a0<a href=\"https:\/\/ashpublications.org\/blood\/article-abstract\/doi\/10.1182\/blood.2025030170\/570175\/Dual-MYC-and-GSPT1-Protein-Degrader-for-MYC-Driven\" rel=\"nofollow noopener\" target=\"_blank\">Blood<\/a>.\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"The\u00a0MYC\u00a0protein\u00a0is\u00a0involved\u00a0in about 70% of cancers, but scientists have\u00a0been unable\u00a0to develop drugs that\u00a0effectively block\u00a0it\u00a0 Researchers discovered a dependent relationship\u00a0in&hellip;\n","protected":false},"author":2,"featured_media":650017,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":"","_share_on_mastodon":"0"},"categories":[78],"tags":[7260,769,90,110,13651,274731,10723,18,11293,135,474,19,17,941,274732],"class_list":["post-650016","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-all-journal-news","tag-biotech","tag-blood","tag-cancer","tag-cancer-center-featured-story-2","tag-cancercancer-researchblood-cancerleukemialymphomamultiple-myelomaacute-myeloid-leukemia-amlmycmyc-inhibitorsmyc-driven-cancersdrug-developmentprotein-degradation","tag-clinical-trials","tag-eire","tag-ethics-and-research-methods","tag-health","tag-healthcare","tag-ie","tag-ireland","tag-newswise","tag-the-university-of-texas-md-anderson-cancer-center"],"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/117136719194540400","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/650016","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=650016"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/650016\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/650017"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=650016"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=650016"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=650016"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}