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Title: | Genomic alterations to guide treatment selection in metastatic prostate cancer. | Authors: | Davies A. ;Azad A.A.;Kwan E.M. | Monash Health Department(s): | Oncology | Institution: | (Davies) Department of Medical Oncology, Monash Health, Melbourne, Australia (Davies, Kwan) Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia (Azad) Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia (Azad) Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia (Kwan) Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada |
Issue Date: | 4-Aug-2022 | Copyright year: | 2022 | Publisher: | Begell House Inc. | Place of publication: | United States | Publication information: | Critical Reviews in Oncogenesis. 27(1) (pp 61-80), 2022. Date of Publication: 2022. | Journal: | Critical Reviews in Oncogenesis | Abstract: | Treatment options for men with metastatic prostate cancer have greatly expanded in the last decade. Androgen receptor pathway inhibitors, taxane cytotoxic therapy, poly(ADP-ribose) polymerase inhibitors, and radionuclide theranostics against prostate-specific membrane antigen have collectively contributed to incremental improvements in both quality and longevity of life for patients with metastatic castration-resistant prostate cancer (mCRPC). Despite these successes, few studies inform on optimal therapy selection and sequencing across this crowded treatment landscape. Genomic analysis of both tissue and liquid biopsy specimens shows promise in bridging this practice gap, with alterations in several key prostate cancer driver genes demonstrating clear associations with clinical outcomes, as well as informing use of novel precision medicine targeted therapies. In this review, we evaluate the current evidence of genomic alterations in various oncogenic signalling pathways as clinical biomarkers in mCRPC, focusing on correlative studies that analysed outcomes based on findings in plasma cell-free DNA. We highlight the pitfalls of interpreting genomic findings in samples with substandard tumour content, and suggest pathologic and disease factors to consider when embarking upon tumour genotyping to guide treatment decisions in metastatic prostate cancer. As access to life-prolonging therapies improves, and barriers to cost-effective genotyping and reliable data interpretation are overcome, we anticipate that predictive and prognostic biomarkers that inform on disease biology, drug sensitivity and therapy resistance will inevitably be integrated into the routine care of patients with metastatic prostate cancer.Copyright © 2022, Begell House Inc.. All rights reserved. | DOI: | http://monash.idm.oclc.org/login?url=https://dx.doi.org/10.1615/CritRevOncog.2022043298 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/48368 | Type: | Article | Subjects: | cancer cancer resistance drug sensitivity genetic marker genotyping life sustaining treatment liquid biopsy metastatic castration resistant prostate cancer molecularly targeted therapy personalized medicine plasma cell prostate cancer signal transduction androgen receptor biological marker chloroplast DNA circulating free DNA phosphatidylinositol 3 kinase |
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