Year: 2015
Type: article
Abstract: A multi-institution integrative sequencing analysis of DNA and RNA from 150 metastatic, castration resistant prostate cancers reveals both known and novel cancer pathways that are clinically actionable, an important step towards precision medicine.Image adapted from the publication.An estimated 220,000 American men are diagnosed with prostate cancer each year, with 30,000 expected to die of it this year.While androgen deprivation therapy (ADT) is initially effective against metastatic disease, most men develop tumors that ultimately become resistant to ADT, including the most recent ADT regimen (abiraterone acetate and enzalutamide).This condition is known as metastatic castration-resistant prostate cancer (mCRPC).While many studies have cataloged somatic alterations in primary prostate cancers, genomic studies of mCRPC have been limited to either autopsy samples or preclinical models.To address the gap in our understanding of mCRPC, an international and multi-institutional consortium that included Fred Hutch investigators and benefitted from key contributions from Dr. Pete Nelson's Laboratory (Human Biology, Clinical Research and Public Health Sciences Divisions), sequenced the DNA and RNA from biopsies of bone or soft tissue metastases prospectively from 150 mCRPC affected individuals.This work was recently published in the journal Cell.This integrative analysis represented an entry point of ongoing clinical trials on combination therapy in mCRPC.The biopsies were obtained from lymph nodes (42%), bone (28.7%), liver (12.7%) as well as other soft tissues (16.7%).Compared to primary prostate tumors, mCRPCs were enriched for mutations in the Androgen Receptor (AR) and the tumor suppressor TP53.Based on both biological and statistical criteria, mCRPCs could be subdivided into discrete molecular subtypes.These subtypes were grouped based on knowledge of biological pathways and alteration clustering
Author: Alexandre Neves
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2625948005