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Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications.

Publication ,  Conference
Kim, W; Small, EJ; Aggarwal, RR; Den, RB; Lehrer, J; Zhang, L; Youngren, J; Goldstein, TC; Alumkal, JJ; Gleave, M; Rettig, M; Evans, CP ...
Published in: Journal of Clinical Oncology
February 20, 2018

197 Background: The PAM50 gene expression classifier (PAM50) identifies luminal and basal subtypes and predicts response to androgen deprivation therapy in localized prostate cancer. The clinical utility of using PAM50 to molecularly subtype mCRPC was evaluated. Methods: PAM50 was applied to RNA expression data from 86 metastatic tumor biopsies from the SU2C-AACR-PCF West Coast Prostate Cancer Dream Team (WCDT; NCT02432001). Overall survival (OS) differences between luminal A (LuA), luminal B (LuB), or basal patients (pts) were determined using Kaplan-Meier analyses. PAM50 was also applied to 15,136 prospectively collected radical prostatectomy (RP) samples from the Decipher GRiD database (NCT02609269). Drug response signatures (DRS) for 89 drugs were derived using publicly available data from the NCI60 cell line panel, and applied to gene expression data from the RP samples to predict patient-specific drug sensitivities. Differences in DRS as a function of PAM50 subtype were assessed using the Pearson’s chi-squared test. Results: The application of PAM50 to mCRPC transcriptional data segregated pts into LuA, LuB, and basal populations (43%, 14%, and 43%, respectively). The median OS for LuA, LuB, and basal pts was 20.6 months, 9.5 months, and 10.4 months, respectively (p=0.04), which was consistent with localized prostate cancer where LuB pts have the worst prognosis. DRS analyses revealed statistically significant differences in drug sensitivities, with LuA and LuB pts predicted to be markedly more sensitive to docetaxel than basal pts (p<0.00001), and basal pts predicted to be markedly more sensitive to platinums and etoposide than LuA and LuB pts (p<0.00001). Conclusions: PAM50 subtyping is prognostic in mCRPC, with LuA pts demonstrating the longest OS. Luminal and basal subtypes have distinct in silico drug response profiles that may be associated with response to mCRPC therapies. Prospective testing of DRS as a biomarker to guide treatment in mCRPC is warranted. Clinical trial information: NCT02432001, NCT02609269.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2018

Volume

36

Issue

6_suppl

Start / End Page

197 / 197

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kim, W., Small, E. J., Aggarwal, R. R., Den, R. B., Lehrer, J., Zhang, L., … Feng, F. Y. (2018). Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications. In Journal of Clinical Oncology (Vol. 36, pp. 197–197). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2018.36.6_suppl.197
Kim, Won, Eric Jay Small, Rahul Raj Aggarwal, Robert Benjamin Den, Jonathan Lehrer, Li Zhang, Jack Youngren, et al. “Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications.” In Journal of Clinical Oncology, 36:197–197. American Society of Clinical Oncology (ASCO), 2018. https://doi.org/10.1200/jco.2018.36.6_suppl.197.
Kim W, Small EJ, Aggarwal RR, Den RB, Lehrer J, Zhang L, et al. Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2018. p. 197–197.
Kim, Won, et al. “Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications.Journal of Clinical Oncology, vol. 36, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 197–197. Crossref, doi:10.1200/jco.2018.36.6_suppl.197.
Kim W, Small EJ, Aggarwal RR, Den RB, Lehrer J, Zhang L, Youngren J, Goldstein TC, Alumkal JJ, Gleave M, Rettig M, Evans CP, Beer TM, Reiter RE, Huang J, Thomas GV, Davicioni E, Ryan CJ, Spratt DE, Feng FY. Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2018. p. 197–197.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2018

Volume

36

Issue

6_suppl

Start / End Page

197 / 197

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences