ArticleThe Journal of clinical investigation2016
Inhibition of CDK4/6 protects against radiation-induced intestinal injury in mice.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
54 citing papers in PubMed, 94 citations in OpenAlex.
- 1,2-propanediol ameliorated radiation-induced intestinal injury in mice.Scientific reports · 2026Article
- B-1a cells mitigate radiation injury by protecting intestinal barrier integrity.Frontiers in immunology · 2026Article
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- Mechanistic pathways predictive modeling and translational interventions for radiation enteritis in cervical cancer radiotherapy.Frontiers in cellular and infection microbiology · 2025Review
- Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway.Translational oncology · 2024Article
- Review
- The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest.NAR cancer · 2024Article
- Therapeutic mechanism of Liangxue-Guyuan-Yishen decoction on intestinal stem cells and tight junction proteins in gastrointestinal acute radiation syndrome rats.Journal of radiation research · 2023Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- Article
- Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells.Oncotarget · 2023Review
- Release of Interferon-β (IFN-β) from ProbioticCancers · 2023Article
- Safety and Feasibility of Radiation Therapy Combined with CDK 4/6 Inhibitors in the Management of Advanced Breast Cancer.Cancers · 2023Article
- Article
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Lactobacillus reuteri Releasing IL-22 (LR-IL-22) Facilitates Intestinal Radioprotection for Whole-Abdomen Irradiation (WAI) of Ovarian Cancer.Radiation research · 2022Article
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
- Intestinal Radiation Protection and Mitigation by Second-Generation ProbioticInternational journal of molecular sciences · 2022Article
- CDK4/6 Inhibition Suppresses p73 Phosphorylation and Activates DR5 to Potentiate Chemotherapy and Immune Checkpoint Blockade.Cancer research · 2022Article
- Mechanisms modulating the activities of intestinal stem cells upon radiation or chemical agent exposure.Journal of radiation research · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Radiotherapy causes dose-limiting toxicity and long-term complications in rapidly renewing tissues, including the gastrointestinal tract. Currently, there is no FDA-approved agent for the prevention or treatment of radiation-induced intestinal injury. In this study, we have shown that PD 0332991 (PD), an FDA-approved selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), prevents radiation-induced lethal intestinal injury in mice. Treating mice with PD or a structurally distinct CDK4/6 inhibitor prior to radiation blocked proliferation and crypt apoptosis and improved crypt regeneration. PD treatment also enhanced LGR5+ stem cell survival and regeneration after radiation. PD was an on-target inhibitor of RB phosphorylation and blocked G1/S transition in the intestinal crypts. PD treatment strongly but reversibly inhibited radiation-induced p53 activation, which blocked p53-upregulated modulator of apoptosis-dependent (PUMA-dependent) apoptosis without affecting p21-dependent suppression of DNA damage accumulation, with a repair bias toward nonhomologous end joining. Further, deletion of PUMA synergized with PD treatment for even greater intestinal radioprotection. Our results demonstrate that the cell cycle critically regulates the DNA damage response and survival of intestinal stem cells and support the concept that pharmacological quiescence is a potentially highly effective and selective strategy for intestinal radioprotection.
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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.