#5: Protein Discovery Offers New Hope for Lethal Prostate Cancer
Identifying the new “weak spots” in the “soft underbelly” of the most aggressive forms of prostate cancer is the ultimate PCF R+D finding. In 2016, two PCF research teams of over 50 scientists, studying a protein called N-Myc, found a major vulnerable new drug target. They found this new weak spot for the neuroendocrine form of prostate cancer (NEPC). Normal cells in the body do not have this weak spot. This lethal, advanced form of NEPC prostate cancer affects up to 25% of men with treatment-resistant disease.
These PCF-funded teams, one led by John Lee, MD (UCLA) and the other by David Rickman, PhD, (Weill Cornell Medicine) discovered that N-Myc regulates the progression of prostate cancer from a typical, treatable, tumor into killer disease. N-Myc is a master cancer cell growth “on-switch.” The teams further found that disrupting N-Myc activity — like turning off a light switch — could actually stop chemotherapy and hormone resistant prostate cancers cold. This new drug research can help not just prostate cancer patients. N-Myc also drives some other human cancers, especially neuroblastoma, a childhood cancer that can be devastating in children.
While still some time from the clinic, these results collectively provide the basis for new, anti-N-Myc precision treatment strategy for men with NEPC that could serve as an alternative to chemotherapy itself with its side effects. PCF is hoping to fast forward anti N-Myc R+D in 2017 as priority for both adult and childhood cancers.
#4: Optimizing Existing Therapies: making current drugs work better for patients
While many research teams focus on discovering new treatments for diseases, finding ways to make existing FDA approved drugs—the end result of years of research, development, and resources—work better for patients is ongoing priority. Improving duration of remissions using existing therapies benefits patients who do not have years to wait for new drugs to come to market.
This past year, PCF Researcher Nima Sharifi, MD (Cleveland Clinic) discovered new—and previously unanticipated—aspects of how next-generation androgen inhibitor abiraterone (Zytiga) is processed in to other “good” and “bad” compounds in the body when patients are treated with the drug. Importantly, his team devised a way to alter abiraterone metabolism to allow the body to make less of the “bad” and more of the “good” breakdown products of the drug. These ideas were then taken right into a ground breaking clinical trial in record time.
These findings hold enormous potential for over 200,000 men in North America and Europe and Australia receiving drugs like abiraterone by measuring and altering abiraterone metabolism.
#3: 1 In 9 Advanced Prostate Cancers Caused By Heritable Genes
This may surprise you: Prostate cancer isn’t just about men anymore. A recent study led by Prostate Cancer Foundation Dream Team member Peter Nelson, MD (Fred Hutchinson Cancer Research Center) has shown that 12% of advanced prostate cancers may be caused by 16 different genes that can be passed down in families. That means women also need to be aware of their family history of prostate cancer because it could put them at greater risk of developing breast, ovarian, and pancreatic cancers.
Breaks in DNA occur thousands of times in each cell cycle, and normal cells have about half a dozen ways to combat DNA damage. However, mutations in DNA damage repair (DDR) genes can lead to the accumulation of mutations that can promote tumor formation. Most notable of these are defects in BRCA1/2 genes, which are infamous for increasing a woman’s risk of breast and ovarian cancer.
These PCF funded and practice-changing findings were reported in the most widely read medical journal in the world, The New England Journal of Medicine. The researchers recommended that all men with metastatic prostate cancer at diagnosis should undergo genetic screening for DDR gene mutations they inherited from their parents. In addition, families of men found to have these DDR mutations should seek genetic counseling for all the children of the prostate cancer patient. Be advised: the type of genetic testing required by patients and their relatives will vary on an individual basis and should be discussed with the doctor who made the diagnosis of prostate cancer.
#2: New Clinical Endpoint will Speed the Delivery of New Drugs to Patients
Prostate cancer can sometimes be slow to progress, frustrating the development of new therapies for patients with early, high-risk disease. New results from ICECaP (Intermediate Clinical Endpoints for Cancer of the Prostate), a PCF-supported initiative led by Dr. Christopher Sweeney (Dana-Farber Cancer Institute), will cut the time required to assess new targeted drug therapies for aggressive prostate cancer by 50%.
Dr. Sweeney and his team identified a new set of clinical trial endpoints that will shorten the time taken to conduct clinical trials and present finding to the FDA. The new “big data” analysis in over 20,000 patients, enables the development of novel therapies that can be administered at the earliest—and potentially most curative—stage possible.
#1 Checkpoint Immunotherapy CAN Work Exceptionally in Prostate Cancer
Checkpoint immunotherapy is a revolutionary cancer treatment for chemotherapy resistant cancers like melanoma, kidney cancer and lung cancer. It had not been carefully studied in prostate cancer patients until 2016. Dr. Julie Graff (Oregon Health & Science University) and her team have reported “exceptional prostate cancer responders” to the checkpoint inhibitor pembrolizumab in prostate cancer patients with enzalutamide resistant cancers. These can occur within 3 months of the start of treatment – but before chemotherapy treatment. In a pioneering study, Dr. Graff found that certain men with advanced, enzalutamide-resistant prostate cancer exhibited exceptional responses to pembrolizumab, with near complete PSA reductions and resolution of metastases on CT scans. Now the PCF Research Enterprise detective work begins. Determining why these prostate cancer patients responded so successfully and durably, is critical for realizing the full capabilities of this potentially curative therapy, and provide life-extending solutions for men with the worst forms of prostate cancer. “Exceptional Responder Research” for antiPD-1 treatment is expanding in the PCF Research Enterprise. PCF currently has 6 research teams in the US and Europe focused on the detective work in making immunotherapy remissions a 100% predictable event for prostate cancer patients. PCF hopes to triple the number of precision immunotherapy R+D teams in 2017.
Please consider donating to further research in 2017.