{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Novoplansky O"],"funding":["United States - Israel Binational Science Foundation","Israel Science Foundation","NCI NIH HHS"],"pagination":["308"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11577641"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(1)"],"pubmed_abstract":["<h4>Background</h4>Basket clinical trials targeting the KRAS<sup>G12C</sup>-mutation in solid tumors have shown initial promise, including in orphan KRAS<sup>G12C</sup> head and neck cancer (HNC). However, development of resistance to KRAS<sup>G12C</sup>-mutant-specific inhibitors (KRAS<sup>G12C</sup>i) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRAS<sup>G12C</sup>i-MRTX849 and AMG510 in a unique syngenic murine KRAS<sup>G12C</sup>-mutated HNC cell line.<h4>Methods</h4>Western-blotting was used for protein abundance and activation, overexpression, and ligand activation studies to verify the intrinsic mechanism of resistance to KRAS<sup>G12C</sup>i in KRAS<sup>G12C</sup>-mutated HNC ce"],"journal":["Journal of experimental & clinical cancer research : CR"],"pubmed_title":["Dual inhibition of HERs and PD-1 counteract resistance in KRAS&lt;sup&gt;G12C&lt;/sup&gt;-mutant head and neck cancer."],"pmcid":["PMC11577641"],"funding_grant_id":["#2021055","BSF","R01 CA247551","700/16","302/21","ISF"],"pubmed_authors":["Shareb RA","Prasad M","Marripati D","Elkabets M","Kong D","Greenshpan Y","Yegodayev KM","Mathukkada S","Novoplansky O","Ben-Lulu T","Bhattacharya B","Bragelmann J","Porgador A","Jagadeeshan S","Gutkind JS"],"additional_accession":[]},"is_claimable":false,"name":"Dual inhibition of HERs and PD-1 counteract resistance in KRAS&lt;sup&gt;G12C&lt;/sup&gt;-mutant head and neck cancer.","description":"<h4>Background</h4>Basket clinical trials targeting the KRAS<sup>G12C</sup>-mutation in solid tumors have shown initial promise, including in orphan KRAS<sup>G12C</sup> head and neck cancer (HNC). However, development of resistance to KRAS<sup>G12C</sup>-mutant-specific inhibitors (KRAS<sup>G12C</sup>i) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRAS<sup>G12C</sup>i-MRTX849 and AMG510 in a unique syngenic murine KRAS<sup>G12C</sup>-mutated HNC cell line.<h4>Methods</h4>Western-blotting was used for protein abundance and activation, overexpression, and ligand activation studies to verify the intrinsic mechanism of resistance to KRAS<sup>G12C</sup>i in KRAS<sup>G12C</sup>-mutated HNC ce","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-02T04:33:10.429Z","creation":"2025-04-04T23:32:17.321Z"},"accession":"S-EPMC11577641","cross_references":{"pubmed":["39567998"],"doi":["10.1186/s13046-024-03227-0"]}}