Personalizing Care for Prostate Cancer
Prostate cancer may still be a leading cause of cancer-related death among men, but Weill Cornell Medical College researchers believe personalized medicine may hold the key to better targeted therapies to reduce that devastating record.
|Dr. Himisha Beltran|
While there are a variety of therapies available to treat — but not cure — prostate cancer, patients often develop a resistance to them, rendering them less effective. The key to developing more effective therapies, said Dr. Himisha Beltran, assistant professor of medicine and assistant professor of medicine in urology at Weill Cornell and oncologist at New York-Presbyterian Hospital/Weill Cornell Medical Center, lies in understanding the unique genetic makeup of each patient's cancer.
"By studying the genomic landscape of prostate cancer," she said, "we can design new, effective therapies that specifically target an individual's altered biological pathways."
Toward this end, Dr. Beltran, who specializes in prostate, bladder, testicular and kidney cancers, has used next-generation sequencing technology to identify mutations in patients with castration-resistant advanced prostate cancer, in collaboration with Dr. Mark A. Rubin, professor of pathology and laboratory medicine and the Homer T. Hirst Professor of Oncology in Pathology at Weill Cornell. Their findings were published recently in the journal European Urology.
For this project, the team joined forces with Foundation Medicine, a cancer diagnostics company based in Cambridge, Mass., that developed a sequencing platform capable of analyzing small amounts of tumor DNA extracted from formalin-fixed, paraffin-embedded biopsy tissue, which is a common way to store samples in pathology labs. By sequencing genomic regions multiple times, the team was able to achieve high accuracy using just a small quantity of DNA.
This approach represents a major technological feat, the researchers say, because traditional sequencing platforms require a large amount of DNA from fresh or frozen tissue samples. Given that patients with prostate cancer typically do not undergo biopsies at advanced stages of the disease, the new technology can instead rely on biopsy tissue acquired during the early diagnostic stage.
"This is the first study to comprehensively look at advanced prostate cancer using small biopsy samples that were not fresh or frozen," said Dr. Beltran, recipient of the Prostate Cancer Foundation Young Investigator Award who joined the Weill Cornell faculty last year. "We demonstrated that this method is clinically feasible, and we believe it will pave the way toward a personalized approach to medicine."
This proof-in-principle study also provided new insights into how patients develop resistance to drugs, including those that target the male hormone androgen. In a subset of aggressive tumors examined by the researchers, the androgen receptor was not expressed, suggesting that these tumors would not respond well to androgen-targeted drugs. Moreover, Dr. Beltran and her team identified novel mutations that could influence sensitivity to a class of drugs called PARP inhibitors, as well as other mutations that could be targeted with existing drugs.
"Our findings highlight the value of next-generation sequencing for predicting each patient's response to therapies and determining the optimal treatment course," Dr. Beltran said. "The entire field of oncology is moving into an era of personalized therapy for patients and tailoring cancer treatments based on a patient's specific molecular alterations, so this approach could have important implications for not just prostate cancer, but also all types of cancer."
December 3, 2012