ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Concomitant MEK and Cyclin Gene Alterations: Implications for Response to Targeted Therapeutics.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- MEK inhibitor-based genomically matched combinatorial targeted therapies in metastatic pancreatic adenocarcinoma with KRAS alterations.The oncologist · 2026Observational
- Plasma cell leukemia: genomic features and their potential relevance for exploring clinical actionability.Blood advances · 2026Article
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- PersonalizedJCO precision oncology · 2025Observational
- Effects of combination therapy of a CDK4/6 and MEK inhibitor in diffuse midline glioma preclinical models.PloS one · 2025Article
- KRAS-Driven Tumorigenesis and KRAS-Driven Therapy in Pancreatic Adenocarcinoma.Molecular cancer therapeutics · 2024Review
- Trametinib in combination with hydroxychloroquine or palbociclib in advanced metastatic pancreatic cancer: data from a retrospective, multicentric cohort (AIO AIO-TF/PAK-0123).Journal of cancer research and clinical oncology · 2024Article
- Treatment ofJournal of gastrointestinal oncology · 2024Article
- If it's a target, it's a pan-cancer target: Tissue is not the issue.Cancer treatment reviews · 2024Review
- Multi-omic analysis in carcinoma of unknown primary (CUP): therapeutic impact of knowing the unknown.Molecular oncology · 2024Article
- Home-run trials for rare cancers: giving the right drug(s) to the right patients at the right time and in the right place.NPJ precision oncology · 2023Review
- Review
- Review
- Article
- Exceptional Response to MEK Inhibition in a Patient With RAF1-Mutant Myxofibrosarcoma: Case Report and Mechanistic Overview.JCO precision oncology · 2023Article
- First-Line Genomic Profiling in Previously Untreated Advanced Solid Tumors for Identification of Targeted Therapy Opportunities.JAMA network open · 2023Observational
- Agnostic Approvals in Oncology: Getting the Right Drug to the Right Patient with the Right Genomics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Complete response to alectinib in ALK-fusion metastatic salivary ductal carcinoma.NPJ precision oncology · 2023Article
- Evolution of the Targeted Therapy Landscape for Cholangiocarcinoma: Is Cholangiocarcinoma the 'NSCLC' of GI Oncology?Cancers · 2023Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeCyclin 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. EXPERIMENTAL
designHerein, we describe 9 patients with advanced malignancies harboring concomitant
resultsTwo patients (with pancreatic cancer) achieved a partial remission (PR) and, overall, 5 patients (56%) had clinical benefit (stable disease ≥ 6 months/PR) with progression-free survival of approximately 7, 9, 9, 11, and 17.5+ months. Interestingly, 1 of these patients whose cancer (gastrointestinal stromal tumor) had progressed on MEK targeting regimen, did well for about 1 year after palbociclib was added.
conclusionsThese observations suggest that cotargeting cyclin and MEK signaling can be successful when tumors bear genomic coalterations that activate both of these pathways. Further prospective studies using this matching precision strategy to overcome resistance are warranted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.