Major international collaboration shows clinically actionable outlook for advanced prostate cancer patients.

A ‘Stand Up to Cancer – Prostate Cancer Foundation Dream Team’, have published the results of their study in Cell. This is the first major genomic study on advanced prostate cancer, and it has presented some very encouraging results.

“This study provides a strong argument that the genomics driving advanced prostate cancer is fundamentally different than primary prostate cancer, and that knowledge of these genomic differences may be immediately clinically actionable for patients with advanced disease,” said Eliezer Van Allen, MD, of Dana-Farber Cancer Institute, a first author of the study.

The study revealed that many patients might be carrying a genetic variant that can either be targeted with existing drugs, or with drugs that should make it to the clinic soon. 

These are very encouraging findings, and are the fruits of a fantastic collaboration across major institutions in the USA and Europe: 

Dana-Farber Cancer Institute, University of Michigan, the Broad Institute, the Beth Israel Deaconess Hospital, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York Presbyterian Hospital, the Fred Hutchinson Cancer Center, the University of Washington, the Institute of Cancer Research in London, the Royal Marsden NHS Foundation Trust in London, Beth Israel Deaconess Cancer Center, Brigham and Women’s Hospital, University of Trento, Italy, Wayne State University School of Medicine, Barbara Ann Karmanos Cancer Institute, and Johns Hopkins School of Medicine.

“This is a landmark paper in several respects,” said Philip Kantoff, MD, leader of the Lank Center for Genitourinary Oncology and chief of Solid Tumor Oncology at Dana-Farber, a senior author of the study. “It represents a model of collaboration between cancer centers, represents a monumental operational, technical and computational achievement and finally represents the value of precision medicine in finding actionable mutations.”

The study will now continue to its next phase. Tumor cells from over 500 patients will be sequenced, as response to treatment and disease progress are monitored.


Integrative Clinical Genomics of Advanced Prostate Cancer

Abstract:Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations inPIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals.