Biomarkers for Programmed Death-1 Inhibition in Prostate Cancer.
Oncologist
; 24(4): 444-448, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30541755
ABSTRACT
Prostate cancer is the second leading cause of cancer death in American men. Despite the common nature of this disease, there is a poor understanding of biomarkers that predict responsiveness to immunotherapeutic agents such as the programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. Herein we describe a case of complete remission with pembrolizumab therapy in a metastatic castrate-resistant prostate cancer patient with a complex germline MSH2 alteration (Boland inversion) in association with a tumor demonstrating high microsatellite instability. Potential utility of high mutational burden assessed by an experimental circulating tumor DNA assay is also shown. The literature concerning biomarkers for PD-1 inhibition is reviewed, including data for various mismatch repair gene deficiencies, microsatellite instability, tumor mutational burden, PD-L1 3' untranslated region mutations, selected POLE mutations, and biallelic CDK12 mutations. Taken together, although prostate cancer is generally believed to be a tumor unresponsive to PD-1 inhibition, careful dissection of tumor biology is able to provide an approach toward predictive biomarkers that has the potential for expanded clinical utility. KEY POINTS Biomarkers for anti-PD1 and anti-PDL1 therapy are poorly defined in prostate cancer.Recent advances are defining new important classes of responsive patients.
Full text:
1
Database:
MEDLINE
Main subject:
Biomarkers, Tumor
/
DNA Repair Enzymes
/
Microsatellite Instability
/
B7-H1 Antigen
/
Programmed Cell Death 1 Receptor
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Prostatic Neoplasms, Castration-Resistant
/
Antineoplastic Agents, Immunological
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Oncologist
Journal subject:
NEOPLASIAS
Year:
2019
Type:
Article
Affiliation country:
United States