ArticleCancer research2022
CDK4/6 Inhibition Suppresses p73 Phosphorylation and Activates DR5 to Potentiate Chemotherapy and Immune Checkpoint Blockade.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Induction chemotherapy plus camrelizumab followed by concurrent chemoradiotherapy in unresectable locally advanced esophageal squamous cell carcinoma: a single-arm phase II trial.Nature communications · 2025Trial
- A DR5/Ligase 3-mediated feedback loop perpetuates immunogenicity in mismatch repair deficient colorectal cancer.Gastroenterology · 2026Article
- Reactivating necroptosis in colorectal cancer potentiates chemotherapy and antitumor immune responses.Cancer letters · 2026Article
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.Science advances · 2025Article
- Predicting immune responsiveness in ER-positive breast cancer for personalized therapy: a population-based study.NPJ precision oncology · 2025Article
- Nanoassemblies loaded with low-dose paclitaxel can enhance the response of lung cancer immunotherapy by activating dendritic cells.Translational lung cancer research · 2025Article
- Review
- Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.Breast (Edinburgh, Scotland) · 2025Review
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- CDK4/6 Inhibitor Resistance in ER+ Breast Cancer.Advances in experimental medicine and biology · 2025Review
- Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives.Bioengineering (Basel, Switzerland) · 2024Review
- CDK4/6 inhibitor abemaciclib combined with low-dose radiotherapy enhances the anti-tumor immune response to PD-1 blockade by inflaming the tumor microenvironment in Rb-deficient small cell lung cancer.Translational lung cancer research · 2024Article
- Article
- Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing to Identify an Immunogenic Cell Death-Related 5-Gene Prognostic Signature in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Article
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Review
- Inhibition of multiple CDKs potentiates colon cancer chemotherapy via p73-mediated DR5 induction.Oncogene · 2023Article
- Challenges to addressing the unmet medical needs for immunotherapy targeting cold colorectal cancer.World journal of gastrointestinal oncology · 2023Article
Corrections and comments
- Commented on by
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Targeting cyclin-dependent kinases 4 and 6 (CDK4/6) is a successful therapeutic approach against breast and other solid tumors. Inhibition of CDK4/6 halts cell cycle progression and promotes antitumor immunity. However, the mechanisms underlying the antitumor activity of CDK4/6 inhibitors are not fully understood. We found that CDK4/6 bind and phosphorylate the p53 family member p73 at threonine 86, which sequesters p73 in the cytoplasm. Inhibition of CDK4/6 led to dephosphorylation and nuclear translocation of p73, which transcriptionally activated death receptor 5 (DR5), a cytokine receptor and key component of the extrinsic apoptotic pathway. p73-mediated induction of DR5 by CDK4/6 inhibitors promoted immunogenic cell death of cancer cells. Deletion of DR5 in cancer cells in vitro and in vivo abrogated the potentiating effects of CDK4/6 inhibitors on immune cytokine TRAIL, 5-fluorouracil chemotherapy, and anti-PD-1 immunotherapy. Together, these results reveal a previously unrecognized consequence of CDK4/6 inhibition, which may be critical for potentiating the killing and immunogenic effects on cancer cells. SIGNIFICANCE: This work demonstrates how inhibition of CDK4/6 sensitizes cancer cells to chemotherapy and immune checkpoint blockade and may provide a new molecular marker for improving CDK4/6-targeted cancer therapies. See related commentary by Frank, p. 1170.
Indexed as
Identifiers
What OpenQuestion holds
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.