Update on Systemic Prostate Cancer Therapies: Management of Metastatic Castration-resistant Prostate Cancer in the Era of Precision Oncology

Chakravarty D, Gao J, Phillips SM, Kundra R, Zhang H, Wang J, Rudolph JE, Yaeger R, Soumerai T, Nissan MH, Chang MT, Chandarlapaty S, Traina TA, Paik PK, Ho AL, Hantash FM, Grupe A, Baxi SS, Callahan MK, Snyder A, Chi P, Danila D, Gounder M, Harding JJ, Hellmann MD, Iyer G, Janjigian Y, Kaley T, Levine DA, Lowery M, Omuro A, Postow MA, Rathkopf D, Shoushtari AN, Shukla N, Voss M, Paraiso E, Zehir A, Berger MF, Taylor BS, Saltz LB, Riely GJ, Ladanyi M, Hyman DM, Baselga J, Sabbatini P, Solit DB, Schultz N. OncoKB: a precision oncology knowledge base. JCO Precis Oncol 2017 Jul;2017 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28890946/ Newton Y, Novak AM, Swatloski T, McColl DC, Chopra S, Graim K, Weinstein AS, Baertsch R, Salama SR, Ellrott K, Chopra M, Goldstein TC, Haussler D, Morozova O, Stuart JM. TumorMap: exploring the molecular similarities of cancer samples in an interactive portal. Cancer Res 2017 Nov 1;77(21):e111-e114 https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29092953/ Seyednasrollah F, Koestler DC, Wang T, Piccolo SR, Vega R, Greiner R, Fuchs C, Gofer E, Kumar L, Wolfinger RD, Winner KK, Bare C, Neto EC, Yu T, Shen L, Abdallah K, Norman T, Stolovitzky G, Soule HR, Sweeney CJ, Ryan CJ, Scher HI, Sartor O, Elo LL, Zhou FL, Guinney J, Costello JC, and Prostate Cancer DREAM Challenge Community. A DREAM challenge to build prediction models for short-term discontinuation of docetaxel in metastatic castration-resistant prostate cancer. JCO Clin Cancer Inform 2017 Aug 4;(1):1-15 http://ascopubs.org/doi/abs/10.1200/CCI.17.00018

Download Full-text

Emerging Subtypes and New Treatments for Castration-Resistant Prostate Cancer

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_100025 ◽

2020 ◽

pp. e319-e332

Author(s):

Benedito A. Carneiro ◽

Tamara L. Lotan ◽

Andre de Souza ◽

Rahul Aggarwal

Keyword(s):

Prostate Cancer ◽

Parp Inhibitors ◽

Phase Iii ◽

Precision Oncology ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Treatment Paradigm ◽

Genomic Characterization ◽

Sequential Treatments ◽

New Treatments

Genomic characterization of metastatic castration-resistant prostate cancer (mCRPC) has been remodeling the treatment landscape of this disease in the past decade. The emergence of molecularly defined subsets of mCRPC is altering the treatment paradigm from therapeutics with nonspecific activity across the spectrum, including androgen receptor (AR)-directed treatments, docetaxel, and cabazitaxel, to targeted approaches directed at molecular subsets of disease. The meaningful benefit of PARP inhibitors in mCRPC carrying mutations in DNA repair genes demonstrated in a phase III trial epitomizes this transition in the treatment paradigm of mCRPC and brings new challenges related to how to sequence and integrate the targeted therapies on top of the treatments with broad activity in all mCRPC. To enable and sustain the advance of precision oncology in the management of mCRPC, genomic characterization is required, including somatic and germline testing, for all patients with the ultimate goal of longitudinal molecular profiling guiding treatment decisions and sequential treatments of this lethal disease. This article reviews the emerging molecular subtypes of mCRPC that are driving the evolution of mCRPC treatment.

Download Full-text