Integrative Genomics of Prostate Cancer Progression
About Integrative Genomics of Prostate Cancer Progression
- Cancer is a disease driven by the continued acquisition of genomic alterations that allow tumor cells to grow and divide abnormally, metastasize to other tissues, and develop resistance to therapies. Understanding the genomic alterations that confer each of these properties is critical for understanding disease evolution and designing optimal therapeutic strategies.
- Dr. Rubin and team are collecting archived primary prostate tumor samples from metastatic castration resistant prostate cancer (mCRPC) patients whose mCRPC tumor genomic and transcriptomic alterations have previously been characterized by the PCF-International Dream Team. Of the 500 patients assessed by the Dream Team, approximately 200 have primary tumor tissue available for this study.
- The genomes and transcriptomes of these ~200 primary tumor samples will be sequenced and compared with alterations in matched metastatic tumors from the same patient in order to identify molecular alterations that mediate drug resistance and progression to mCRPC in individual patients.
- Because of the continual acquisition of genomic mutations, tumors are heterogeneous and can be “multi-focal.” This results in multiple tumor clones with different disease potentials that arise independently. Multiple regions of the primary tumor will be analyzed by these methods in order to identify the tumor clone that ultimately results in mCRPC.
What this means for patients: Despite significant progress made in characterizing the “genomic landscapes” of primary prostate cancer and metastatic castrate resistant prostate cancer (mCRPC), studies have not yet been performed to identify the molecular alterations that mediate progression from primary cancer to mCRPC in patients. Dr. Rubin and team will analyze matched primary tumor and metastatic castration resistant prostate cancer (mCRPC) specimens in order to identify these alterations. If successful, this project will identify molecular mediators and molecular pathways of prostate cancer progression that may serve as therapeutic targets and/or biomarkers that inform optimal therapies for individual patients.
Mark Rubin, MD (Weill Cornell Medical College), Scott Tomlins, MD, PhD (University of Michigan) & Ronglai Shen, PhD (MSKCC)
Joanna Cytra, MD (Weill Cornell Medical College)