A recent FDA approval supported by Stand Up To Cancer research provides a new treatment option for patients with an aggressive form of prostate cancer. The drug, called olaparib, is a precision therapy that targets certain molecular qualities of advanced prostate cancer in patients with genetic mutations that often lead to aggressive cancers, including BRCA1 and BRCA2.
A collaborative 'Dream Team' of scientists funded by Stand Up To Cancer and the Prostate Cancer Foundation contributed to the research that led to the approval of olaparib for advanced prostate cancer.
I'm delighted that the Dream Team's work has led to a therapy that will impact patients with aggressive forms of prostate cancer. Our research was the first to demonstrate that over 20% of patients with metastatic prostate cancer have mutations in genes such as BRCA1 or BRCA2 and that over 10% of these mutations are inherited, which led to the clinical trials that tested olaparib as a potential treatment for these patients."
Arul Chinnaiyan, MD, Ph.D. Dream Team leader and professor of Pathology and Urology at the University of Michigan
Prostate cancer is the second most common cancer in American men, following skin cancer. Furthermore, black men are at increased risk of a prostate cancer diagnosis, and significantly greater risk of dying from prostate cancer compared to whites. In 2020, close to 200,000 men will be diagnosed with new cases of prostate cancer, and about 33,000 men will die from the disease. A common therapy for prostate cancer lowers the levels of male hormones in the body with drugs or by removal of the testes. However, some men develop castration-resistant disease, meaning that the cancer is able to grow and continue to spread despite hormone therapy. As the cancer grows, it may also metastasize to parts of the body outside the prostate.
"New treatments are urgently needed for metastatic castration-resistant prostate cancer, which is particularly aggressive and difficult to treat," said SU2C Scientific Advisory Committee Vice-Chair William Nelson, MD, PhD, director of the Sidney Kimmel Comprehensive Cancer Research, Johns Hopkins University and a recognized expert in prostate cancer. "Stand Up To Cancer is proud to have contributed to the development of this targeted treatment option for people whose prostate cancer has progressed to this stage."
Uncovering the genetic and molecular characteristics of metastatic castration-resistant prostate cancer is key to finding novel treatments. The Dream Team analyzed DNA from metastatic castration-resistant prostate cancer samples gathered from eight clinical trials. In a study published in the journal Cell, the team showed that several genetic mutations, including BRCA1 and BRCA2, are prevalent in 23% of patients with metastatic castration-resistant prostate cancer.
"Prior to our research, certain genetic mutations such as BRCA1 were connected mainly to breast and ovarian cancer," said Chinnaiyan. "Our findings led us to question if drugs utilized for BRCA-positive breast and ovarian cancers - such as olaparib - could also be utilized for prostate cancer patients with the same genetic mutations, which launched an effort to test olaparib in clinical trials for men with prostate cancer."
Chinnaiyan and the Dream Team presented their initial findings at the annual SU2C Scientific Summit in 2015. Another Dream Team of SU2C scientists focused on women's cancers immediately offered data from prior testing of drugs, including olaparib, that have been used successfully for women's cancers with the same BRCA1 and BRCA2 mutations. "This type of collaboration is characteristic of SU2C," said Sung Poblete, PhD, RN, SU2C CEO. "Sharing this data saved the Prostate Cancer Dream Team nearly $500,000 and six months of work, allowing this compelling research to be accelerated to benefit patients faster."
Collaborating with colleagues testing olaparib in a clinical trial, the Dream Team analyzed each patient's DNA for the genetic mutations they had identified in their previous studies. The trial results, published in the New England Journal of Medicine, revealed that metastatic castration-resistant prostate cancer patients with genetic mutations such as BRCA1 and BRCA2 often responded preferentially to olaparib. These results led to olaparib receiving a 'Breakthrough Therapy Designation' from the FDA, which laid the groundwork for the recent FDA approval of olaparib in metastatic prostate cancer.
Olaparib is a type of drug called a PARP inhibitor. PARP is a group of enzymes used by cells to repair damaged DNA. Olaparib suppresses PARP's function, which inhibits DNA repair in cells with genetic DNA repair mutations such as BRCA1 or BRCA2. In many cases, this causes the cells with DNA repair mutations to die while sparing healthy cells.
The FDA approved olaparib for homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer on May 19, 2020.
The research that supported this FDA approval was funded in part by the SU2C?Prostate Cancer Foundation Prostate Dream Team: Precision Therapy of Advanced Prostate Cancer.
The Dream Team focused on women's cancers that contributed drug testing data was the SU2C PI3K Dream Team: Targeting the PI3K Pathway in Women's Cancers.
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