ArticleCell death & disease2019
Cisplatin exposure causes c-Myc-dependent resistance to CDK4/6 inhibition in HPV-negative head and neck squamous cell carcinoma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Palbociclib, a Selective CDK4/6 Inhibitor, Administered Before and After Chemoradiotherapy for Human Papillomavirus-Negative, Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm, Phase II Trial.JCO precision oncology · 2025Trial
- Palbociclib and cetuximab in cetuximab-resistant human papillomavirus-related oropharynx squamous-cell carcinoma: A multicenter phase 2 trial.Oral oncology · 2021Trial
- Article
- Molecular Mechanisms of FAT Atypical Cadherin 1 (FAT1), the Hippo Pathway, and the Yes-Associated Protein (YAP) Signaling Pathways in Some Cancers.Asian Pacific journal of cancer prevention : APJCP · 2026Review
- Deciphering the differential impact of CDK4 mutations on abemaciclib binding in oral squamous cell carcinoma: a precision medicine approach.Irish journal of medical science · 2025Article
- Cisplatin resistance in head and neck squamous cell carcinoma is linked to DNA damage response and cell cycle arrest transcriptomics rather than poor drug uptake.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Targeting CDK2 to combat drug resistance in cancer therapy.Future oncology (London, England) · 2024Review
- Necroptosis and autophagy in cisplatinum-triggered nephrotoxicity: Novel insights regarding their prognostic and diagnostic potential.Toxicology reports · 2024Article
- HNCDrugResDb: a platform for deciphering drug resistance in head and neck cancers.Scientific reports · 2024Article
- Evolution of Treatment Strategies for Gestational Trophoblastic Neoplasia: Chemotherapy, Immunotherapy, and Molecular Targeted Therapy.Current treatment options in oncology · 2024Review
- Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer.NPJ precision oncology · 2024Article
- Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance.International journal of clinical and experimental pathology · 2024Review
- Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma.Theranostics · 2024Article
- Editorial of Special Issue "Oral Cancer: From Pathophysiology to Novel Therapeutic Approaches".Biomedicines · 2023Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- Proliferative exhausted CD8eLife · 2023Article
- P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization.Journal of translational medicine · 2023Article
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Article
- The diverse functions of FAT1 in cancer progression: good, bad, or ugly?Journal of experimental & clinical cancer research : CR · 2022Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The loss of p16 is a signature event in Human Papilloma Virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) that leads to increased Cyclin Dependent Kinase 4/6 (CDK) signaling. Palbociclib, a CDK4/6 inhibitor, is active for the treatment of a subset of HNSCC. In this study, we analyzed patient response data from a phase I clinical trial of palbociclib in HNSCC and observed an association between prior cisplatin exposure and CDK inhibitor resistance. We studied the effects of palbociclib on cisplatin-sensitive and -resistant HNSCC cell lines. We found that while palbociclib is highly effective against chemo-naive HNSCC cell lines and tumor xenografts, prior cisplatin exposure induces intrinsic resistance to palbociclib in vivo, a relationship that was not observed in vitro. Mechanistically, in the course of provoking a DNA damage-resistance phenotype, cisplatin exposure upregulates both c-Myc and cyclin E, and combination treatment with palbociclib and the c-Myc bromodomain inhibitor JQ1 exerts a synergistic anti-growth effect in cisplatin-resistant cells. These data show the benefit of exploiting the inherent resistance mechanisms of HNSCC to overcome cisplatin- and palbociclib resistance through the use of c-Myc inhibition.
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