ArticleCell reports2020
Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 286 citations in OpenAlex.
- Novel Therapeutic Strategies for Metastatic Prostate Cancer Care.European urology · 2025Pooled it
- Development and prevalence of castration-resistant prostate cancer subtypes.Neoplasia (New York, N.Y.) · 2020Pooled it
- A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC).Prostate cancer and prostatic diseases · 2025Trial
- Neoadjuvant fuzuloparib combined with abiraterone for localized high-risk prostate cancer (FAST-PC): A single-arm phase 2 study.Cell reports. Medicine · 2025Trial
- Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small Cell Lung Cancer: The Phase II BALTIC Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- IRE1 activity is prognostic in localised and metastatic prostate cancer and affects epithelial lineage states.EMBO molecular medicine · 2026Article
- Combined BET bromodomain and DNA methyltransferase inhibition targets critical survival pathways in transdifferentiated prostate cancer.JCI insight · 2026Article
- Senolytic Interventions Enhance the Anti-metastatic Activity of Chemotherapy in Prostate Cancer.Cancer research · 2026Article
- mRNA-based therapeutics in lung Cancer: Mechanisms, applications, and translational challenges.Journal, genetic engineering & biotechnology · 2026Review
- Increasing Cancer Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival.bioRxiv : the preprint server for biology · 2026Article
- Genotoxic antibody-drug conjugates combined with BCL-XL inhibitors enhance therapeutic efficacy in metastatic castration-resistant prostate cancer.The Journal of clinical investigation · 2026Article
- ADT and activation of HGF and WNT axes in double-null prostate cancer.Nature reviews. Urology · 2026Review
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- Large-scale Genomic Landscape and Clinical Outcomes of De Novo and Treatment-emergent Neuroendocrine Prostate Cancer.European urology open science · 2026Article
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- Review
- PSA Response as a Prognostic Marker in Metastatic Hormone-sensitive Prostate Cancer: Comparison with Tumor Volume (CHAARTED).European urology open science · 2026Article
- Decoding the association between platinum resistance and HPV status in cervical cancer using organoid models.BMC biology · 2026Article
- Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Targeting arginine metabolism overcomes chemotherapy resistance in aggressive-variant prostate cancers.iScience · 2026Article
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Prostate cancers (PCs) with loss of the potent tumor suppressors TP53 and RB1 exhibit poor outcomes. TP53 and RB1 also influence cell plasticity and are frequently lost in PCs with neuroendocrine (NE) differentiation. Therapeutic strategies that address these aggressive variant PCs are urgently needed. Using deep genomic profiling of 410 metastatic biopsies, we determine the relationships between combined TP53 and RB1 loss and PC phenotypes. Notably, 40% of TP53/RB1-deficient tumors are classified as AR-active adenocarcinomas, indicating that NE differentiation is not an obligate consequence of TP53/RB1 inactivation. A gene expression signature reflecting TP53/RB1 loss is associated with diminished responses to AR antagonists and reduced survival. These tumors exhibit high proliferation rates and evidence of elevated DNA repair processes. While tumor cells lacking TP53/RB1 are highly resistant to all single-agent therapeutics tested, the combination of PARP and ATR inhibition is found to produce significant responses, reflecting a clinically exploitable vulnerability resulting from replication stress.
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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.