ArticleThe oncologist2021
Tumor Frameshift Mutation Proportion Predicts Response to Immunotherapy in Mismatch Repair-Deficient Prostate Cancer.
Article in The oncologist, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study.Prostate cancer and prostatic diseases · 2025Trial
- Chimeric MHC class I- and II-restricted non-self epitopes broaden antitumor T cell reactions.The Journal of experimental medicine · 2026Article
- Biomarkers in metastatic castration-resistant prostate cancer for efficiency of immune checkpoint inhibitors.Annals of medicine · 2025Review
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
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- Article
- Evidence-Based Recommendations on the Use of Immunotherapies and Monoclonal Antibodies in the Treatment of Male Reproductive Cancers.Current oncology (Toronto, Ont.) · 2025Review
- Immunotherapy in metastatic prostate cancer.Therapeutic advances in medical oncology · 2025Review
- Identification of shared neoantigens derived from frameshift mutations in theFrontiers in immunology · 2025Article
- Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025Article
- Intratumoral heterogeneity drives acquired therapy resistance in a patient with metastatic prostate cancer.NPJ precision oncology · 2024Article
- Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Frameshift Mutations in Leukemia-Associated Genes Correlate With Superior Outcomes in Patients Undergoing Allogeneic Stem Cell Transplant forJournal of hematology · 2024Article
- Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis.Journal of personalized medicine · 2024Article
- Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients.Journal of experimental & clinical cancer research : CR · 2024Review
- A Panel-Based Mutational Signature of Mismatch Repair Deficiency is Associated With Durable Response to Pembrolizumab in Metastatic Castration-Resistant Prostate Cancer.Clinical genitourinary cancer · 2024Article
- Cooling inflammation while potentiating immune checkpoint inhibition: Enhancing the benefit-risk ratio of immuno-oncology therapy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer.NPJ genomic medicine · 2024Article
- Immunogenomic Landscape of Neuroendocrine Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Predicting the Abscopal Effect: Associated Tumor Histologic Subtypes and Biomarkers.Molecular cancer therapeutics · 2023Review
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundGenomic biomarkers that predict response to anti-PD1 therapy in prostate cancer are needed. Frameshift mutations are predicted to generate more neoantigens than missense mutations; therefore, we hypothesized that the number or proportion of tumor frameshift mutations would correlate with response to anti-PD1 therapy in prostate cancer.
methodsTo enrich for response to anti-PD1 therapy, we assembled a multicenter cohort of 65 men with mismatch repair-deficient (dMMR) prostate cancer. Patient characteristics and outcomes were determined by retrospective chart review. Clinical somatic DNA sequencing was used to determine tumor mutational burden (TMB), frameshift mutation burden, and frameshift mutation proportion (FSP), which were correlated to outcomes on anti-PD1 treatment. We subsequently used data from a clinical trial of pembrolizumab in patients with nonprostatic dMMR cancers of various histologies as a biomarker validation cohort.
resultsNineteen of 65 patients with dMMR metastatic castration-resistant prostate cancer were treated with anti-PD1 therapy. The PSA
conclusionTumor FSP correlated with prolonged efficacy of anti-PD1 treatment among patients with dMMR cancers and may represent a new biomarker of immune checkpoint inhibitor sensitivity. IMPLICATIONS FOR PRACTICE: Given the modest efficacy of immune checkpoint inhibition (ICI) in unselected patients with advanced prostate cancer, biomarkers of ICI sensitivity are needed. To facilitate biomarker discovery, a cohort of patients with DNA mismatch repair-deficient (dMMR) prostate cancer was assembled, as these patients are enriched for responses to ICI. A high response rate to anti-PD1 therapy in these patients was observed; however, these responses were not durable in most patients. Notably, tumor frameshift mutation proportion (FSP) was identified as a novel biomarker that was associated with prolonged response to anti-PD1 therapy in this cohort. This finding was validated in a separate cohort of patients with nonprostatic dMMR cancers of various primary histologies. This works suggests that FSP predicts response to anti-PD1 therapy in dMMR cancers, which should be validated prospectively in larger independent cohorts.
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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.