ArticleOncogene2020
Chemotherapy impacts on the cellular response to CDK4/6 inhibition: distinct mechanisms of interaction and efficacy in models of pancreatic cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer.NPJ breast cancer · 2025Article
- RB loss sensitizes triple-negative breast cancer to apoptosis induced by cellular stress.Cell death discovery · 2025Article
- Ribociclib in Sequential Combination with Doxorubicin in Anthracycline-Naïve Advanced Soft-Tissue Sarcomas: Results of a Dose-Finding Phase Ib Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors.BJC reports · 2025Article
- CDK2 inhibition sensitizes anthracycline-induced immunogenic cell death and enhances the efficacy of anti-PD-1 therapy.Frontiers in immunology · 2025Article
- A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors.Research square · 2024Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- The Extracellular Niche and Tumor Microenvironment Enhance KRAS Inhibitor Efficacy in Pancreatic Cancer.Cancer research · 2024Article
- Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Combination of Ribociclib and Gemcitabine for the Treatment of Medulloblastoma.Molecular cancer therapeutics · 2022Article
- RB loss determines selective resistance and novel vulnerabilities in ER-positive breast cancer models.Oncogene · 2022Article
- Network controllability solutions for computational drug repurposing using genetic algorithms.Scientific reports · 2022Article
- Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines.Frontiers in pharmacology · 2022Article
- The Role of CDK4 in the Pathogenesis of Pancreatic Cancer.Healthcare (Basel, Switzerland) · 2021Article
- Modeling pancreatic cancer in mice for experimental therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways.Cell biology and toxicology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease characterized by the aberrations in multiple genes that drive pathogenesis and limit therapeutic response. While CDK4/6 represents a downstream target of both KRAS mutation and loss of the CDKN2A tumor suppressor in PDAC, clinical and preclinical studies indicate that pharmacological CDK4/6 inhibitors are only modestly effective. Since chemotherapy represents the established backbone of PDAC treatment we evaluated the interaction of CDK4/6 inhibitors with gemcitabine and taxanes that are employed in the treatment of PDAC. Herein, we demonstrate that the difference in mechanisms of actions of chemotherapeutic agents elicit distinct effects on the cellular response to CDK4/6 inhibition. Gemcitabine largely ablates the function of CDK4/6 inhibition in S-phase arrested cells when administered contemporaneously; although, when cells recover from S-phase block they exhibit sensitivity to CDK4/6 inhibition. In contrast, pharmacological inhibition of CDK4/6 yields a cooperative cytostatic effect in combination with docetaxel and prevents adaptation and cell cycle re-entry, which is a common basis for resistance to such agents. Importantly, using organoid and PDX models we could confirm the cooperative effects between chemotherapy and CDK4/6 inhibition in vivo. These data indicate that the combination of cytotoxic and cytostatic agents could represent an important modality in those tumor types that are relatively resistant to CDK4/6 inhibitors.
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Registered trials
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.