ArticleCancer research2014
CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 116 citations in OpenAlex.
- Phase II trial of palbociclib in patients with metastatic urothelial cancer after failure of first-line chemotherapy.British journal of cancer · 2018Trial
- Review
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- Case Report: Acquired CDKN2A/B deletion and mTOR inhibitor resistance in TSC2-mutant metastatic epithelioid angiomyolipoma.Frontiers in medicine · 2026Article
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment.Frontiers in pharmacology · 2025Review
- Article
- Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives.World journal of gastrointestinal oncology · 2023Review
- Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition.International journal of molecular sciences · 2023Review
- Blockage of retinoic acid signaling via RARγ suppressed the proliferation of pancreatic cancer cells by arresting the cell cycle progression of the G1-S phase.Cancer cell international · 2023Article
- Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023Review
- Review
- Insights into the Peritumoural Brain Zone of Glioblastoma:International journal of molecular sciences · 2023Article
- Combination Therapies with CDK4/6 Inhibitors to Treat KRAS-Mutant Pancreatic Cancer.Cancer research · 2023Article
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
- Targeting CDK4/6 for Anticancer Therapy.Biomedicines · 2022Review
- Cuprotosis-Related Genes: Predicting Prognosis and Immunotherapy Sensitivity in Pancreatic Cancer Patients.Journal of oncology · 2022Article
- The Role of Inherited Pathogenic CDKN2A Variants in Susceptibility to Pancreatic Cancer.Pancreas · 2021Review
- Global Phosphoproteomics Reveal CDK Suppression as a Vulnerability to KRas Addiction in Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- A novel cystathionine γ-lyase inhibitor, I194496, inhibits the growth and metastasis of human TNBC via downregulating multiple signaling pathways.Scientific reports · 2021Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations in p16(INK4A) (CDKN2A) occur in approximately 80% of sporadic pancreatic ductal adenocarcinoma (PDAC), contributing to its early progression. Although this loss activates the cell-cycle-dependent kinases CDK4/6, which have been considered as drug targets for many years, p16(INK4A)-deficient PDAC cells are inherently resistant to CDK4/6 inhibitors. This study searched for targeted therapies that might synergize with CDK4/6 inhibition in this setting. We report that the IGF1R/IR inhibitor BMS-754807 cooperated with the CDK4/6 inhibitor PD-0332991 to strongly block proliferation of p16(INK4A)-deficient PDAC cells in vitro and in vivo. Sensitivity to this drug combination correlated with reduced activity of the master cell growth regulator mTORC1. Accordingly, replacing the IGF1R/IR inhibitor with the rapalog inhibitor temsirolimus broadened the sensitivity of PDAC cells to CDK4/6 inhibition. Our results establish targeted therapy combinations with robust cytostatic activity in p16(INK4A)-deficient PDAC cells and possible implications for improving treatment of a broad spectrum of human cancers characterized by p16(INK4A) loss.
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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.