{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Maertens O"],"funding":["Children&apos;s Hospital Boston","Ludwig Center at Harvard","Ludwig center at Harvard","Howard Hughes Medical Institute","NCI NIH HHS","HHS | NIH | National Cancer InstituteHHS | NIH | National Cancer Institute (NCI)"],"pagination":["526-545"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10151004"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(4)"],"pubmed_abstract":["Although the majority of <i>BRAF</i>-mutant melanomas respond to BRAF/MEK inhibitors, these agents are not typically curative. Moreover, they are largely ineffective in <i>NRAS</i>- and <i>NF1</i>-mutant tumors. Here we report that genetic and chemical suppression of HDAC3 potently cooperates with MAPK pathway inhibitors in all three RAS pathway-driven tumors. Specifically, we show that entinostat dramatically enhances tumor regression when combined with BRAF/MEK inhibitors, in both models that are sensitive or relatively resistant to these agents. Interestingly, <i>MGMT</i> expression predicts responsiveness and marks tumors with latent defects in DNA repair. BRAF/MEK inhibitors enhance these defects by suppressing homologous recombination genes, inducing a BRCA-like state; however, addit"],"journal":["Cancer discovery"],"pubmed_title":["MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in <i>BRAF-, NRAS</i>-, and <i>NF1</i>-Mutant Melanomas."],"pmcid":["PMC10151004"],"funding_grant_id":["R01CA111754","R01 CA111754"],"pubmed_authors":["Gavin AG","Manchester HE","Kuzmickas R","Elledge SJ","Hatchi E","Pathania S","Guild CJ","Flaherty KT","Maertens O","De Raedt T","Garraway LA","Emerson CE","Wong TC","Bowman-Colin C","Cichowski K"],"additional_accession":[]},"is_claimable":false,"name":"MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in <i>BRAF-, NRAS</i>-, and <i>NF1</i>-Mutant Melanomas.","description":"Although the majority of <i>BRAF</i>-mutant melanomas respond to BRAF/MEK inhibitors, these agents are not typically curative. Moreover, they are largely ineffective in <i>NRAS</i>- and <i>NF1</i>-mutant tumors. Here we report that genetic and chemical suppression of HDAC3 potently cooperates with MAPK pathway inhibitors in all three RAS pathway-driven tumors. Specifically, we show that entinostat dramatically enhances tumor regression when combined with BRAF/MEK inhibitors, in both models that are sensitive or relatively resistant to these agents. Interestingly, <i>MGMT</i> expression predicts responsiveness and marks tumors with latent defects in DNA repair. BRAF/MEK inhibitors enhance these defects by suppressing homologous recombination genes, inducing a BRCA-like state; however, addit","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Apr","modification":"2026-05-29T03:06:07.28Z","creation":"2025-02-19T02:39:12.664Z"},"accession":"S-EPMC10151004","cross_references":{"pubmed":["30709805"],"doi":["10.1158/2159-8290.cd-18-0879","10.1158/2159-8290.CD-18-0879"]}}