{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kato S"],"funding":["NCI","NCI NIH HHS","NIH"],"pagination":["2792-2797"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11005753"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(10)"],"pubmed_abstract":["<h4>Purpose</h4>Cyclin and MAPK/MEK-related gene alterations are implicated in cell-cycle progression and cancer growth. Yet, monotherapy to target the cyclin (CDK4/6) or the MEK pathway has often yielded disappointing results. Because coalterations in cyclin and MEK pathway genes frequently cooccur, we hypothesized that resistance to CDK4/6 or MEK inhibitor monotherapy might be mediated via activation of oncogenic codrivers, and that combination therapy might be useful.<h4>Experimental design</h4>Herein, we describe 9 patients with advanced malignancies harboring concomitant <i>CDKN2A</i> and/or <i>CDKN2B</i> alterations (upregulate CDK4/6) along with <i>KRAS</i> or <i>BRAF</i> alterations (activate the MEK pathway) who were treated with palbociclib (CDK4/6 inhibitor) and trametinib (MEK "],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["Concomitant MEK and Cyclin Gene Alterations: Implications for Response to Targeted Therapeutics."],"pmcid":["PMC11005753"],"funding_grant_id":["K08 CA168999","R21 CA192072","K08CA168999","P30 CA023100","R21CA192072"],"pubmed_authors":["Okamura R","Lee S","Shaya J","Sicklick JK","Kurzrock R","Jimenez RE","Kato S","Adashek JJ"],"additional_accession":[]},"is_claimable":false,"name":"Concomitant MEK and Cyclin Gene Alterations: Implications for Response to Targeted Therapeutics.","description":"<h4>Purpose</h4>Cyclin and MAPK/MEK-related gene alterations are implicated in cell-cycle progression and cancer growth. Yet, monotherapy to target the cyclin (CDK4/6) or the MEK pathway has often yielded disappointing results. Because coalterations in cyclin and MEK pathway genes frequently cooccur, we hypothesized that resistance to CDK4/6 or MEK inhibitor monotherapy might be mediated via activation of oncogenic codrivers, and that combination therapy might be useful.<h4>Experimental design</h4>Herein, we describe 9 patients with advanced malignancies harboring concomitant <i>CDKN2A</i> and/or <i>CDKN2B</i> alterations (upregulate CDK4/6) along with <i>KRAS</i> or <i>BRAF</i> alterations (activate the MEK pathway) who were treated with palbociclib (CDK4/6 inhibitor) and trametinib (MEK ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2026-05-29T17:44:58.355Z","creation":"2026-04-08T05:41:23.68Z"},"accession":"S-EPMC11005753","cross_references":{"pubmed":["33472910"],"doi":["10.1158/1078-0432.CCR-20-3761","10.1158/1078-0432.ccr-20-3761"]}}