Accelerating precision medicine in metastatic prostate cancer

Abstract

Despite advances in the screening and treatment of prostate cancer, the therapy options available, particularly for later stages of the disease, remain limited, and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in considerable variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach for identifying patients whose tumors exhibit actionable targets and for making more informed treatment decisions. Here we discuss how precision oncology can be accelerated to inform broader genomically driven clinical decisions for men with advanced prostate cancer, to inform drug development and, ultimately, to contribute to new treatment paradigms.

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Fig. 1: The unmet need of precision medicine across different clinical states of prostate cancer.
Fig. 2: Current therapeutic landscape for different clinical states of advanced forms of prostate cancer.
Fig. 3: Proposed workflow for the implementation of genomic testing in prostate cancer in clinical practice, from sample acquisition to clinical decision-making.
Fig. 4: Learning from exceptional responders.

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Conception and design, all authors; analysis and interpretation of data, all authors; first draft of the manuscript, J.M., R.M., W.A. and H.B.; review and critical edits to the manuscript, all authors; final approval of the manuscript, all authors; study supervision, H.B.

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Correspondence to Himisha Beltran.

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Competing interests

J.M. reports advisory board participation for Amgen, AstraZeneca, Roche, Janssen, MSD and Clovis Oncology; and research funding from AstraZeneca and Pfizer Oncology. R.M. received research funding from Bayer, Pfizer and Tempus; serves on advisory board for Bayer, Bristol Myers Squib, Exelixis, Janssen, Novartis, Pfizer, Sanofi and Tempus; and is a consultant for Dendreon and Vividion. W.A. reports consulting/advisory for Clovis, Janssen, More Health, ORIC and Daiichi Sankyo; research funding from AstraZeneca, Zenith Epigenetics, Clovis, GlaxoSmithKline, ORIC and Epizyme; travel from GlaxoSmithKline, Clovis and ORIC; and honoraria from CARET. R.A. reports advisory board participation and research funding from Merck, AstraZeneca and Janssen. B.M. reports research funding from AstraZeneca, Janssen, Clovis, Astellas and Beigene. M.R. reports consulting for Amgen, Ambryx and Constellation; educational writing and consulting for Plexus; speaking for Bayer and Janssen; and funding and clinical research support from Novartis, Astellas, Medivation and Merck. D.S. has consulted for/received honoraria from Pfizer, Loxo Oncology, Lilly Oncology, BioBridge, Vivideon Therapeutics and Illumina. E.V.A. reports advisory/consulting from Tango Therapeutics, Genome Medical, Invitae, Enara Bio, Janssen, Manifold Bio and Monte Rosa; research support from Novartis and BMS; equity in Tango Therapeutics, Genome Medical, Syapse, Enara Bio, Manifold Bio, Microsoft and Monte Rosa; travel reimbursement from Roche/Genentech; and institutional patents on chromatin mutations and immunotherapy response, and methods for clinical interpretation. D.V. reports honoraria from Clovis Oncology. H.B. reports advisory/consulting from Janssen, Amgen, Astra Zeneca, Pfizer, Astellas and Sanofi Genzyme; and research funding from Janssen, Abbvie Stemcentryx, Eli Lilly, Millenium and Astellas. J.V. is employed by the Prostate Cancer Clinical Trials Consortium. H.R.S., J.W.S. and A.K.M. are employed by the Prostate Cancer Foundation.

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Mateo, J., McKay, R., Abida, W. et al. Accelerating precision medicine in metastatic prostate cancer. Nat Cancer 1, 1041–1053 (2020). https://doi.org/10.1038/s43018-020-00141-0

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