“We have for the first time produced a comprehensive genetic map of the mutations in prostate cancers that have spread round the body,” explained co-author Johann de Bono, M.D., Ph.D., professor of experimental cancer medicine at ICR. “This map will guide our future treatment and trials for this group of different lethal diseases. We’re describing this study as prostate cancer’s Rosetta stone—because of the ability it gives us to decode the complexity of the disease, and to translate the results into personalized treatment plans for patients.
The findings from this study were released today in Cell through an article entitled “Integrative Clinical Genomics of Advanced Prostate Cancer.”
The investigators believe that physicians could begin testing for these clinically actionable markers and give patients with advanced prostate cancer existing drugs or drug combinations targeted at these genomic aberrations within their tumors.
The ICR researchers and their collaborators isolated samples form 150 patients with advanced prostate cancer and analyzed the genetic code from metastatic tumors within their lymph nodes, liver, soft tissues, and bone.
Interestingly, the researchers found that nearly two thirds of the patients had mutations in a molecule that interacts with the male hormone androgen, which is targeted by current standard treatments—possibly leading to new therapies for hormone therapy.
“Our study shines new light on the genetic complexity of prostate cancer as it develops and spreads—revealing it to be not a single disease, but many diseases each driven by their own set of mutations,” said Dr. de Bono. “What’s hugely encouraging is that many of the key mutations we have identified are ones targeted by existing cancer drugs—meaning that we could be entering a new era of personalized cancer treatment.”
Additionally, the study found mutations in the BRCA1 and BRCA2 genes, which have been successfully treated using PARP inhibitors for breast cancer patients. Moreover, the researchers discovered new mutations that had never been detected before in the PI3K and RAF gene families, which could be targeted by existing chemotherapeutic drugs.
The ICR scientists also found a small percentage of the patients were born with DNA errors that predisposed them to prostate cancer—strengthen the case for genetic screening for people with a family history of the disease.
“Cancer becomes lethal at the stage when it spreads round the body and stops responding to treatment—but until now it has been incredibly difficult to find out exactly what is going on genetically at that critical point” said Paul Workman, Ph.D., chief executive and president of ICR. “This major new study opens up the black box of metastatic cancer, and has found inside a wealth of genetic information that I believe will change the way we think about and treat advanced disease.”