Top 5 Discoveries of 2015 Mean More Lives Saved in 2016

A Great Leap Forward

While every year brings new discoveries and greater understanding, 2015 stands out as an exceptional year for science. And not just science—genetics-based science that will, in the very near future, directly affect the care and improve the outcome for thousands, if not millions, of prostate cancer patients worldwide. Not since we reported the approval of six new drugs in just four years in 2013 are we seeing the potential for more lives lived longer, better, and more fully. What’s most exciting is that PCF’s efforts to treat prostate cancer precisely according to its myriad genetic profiles is helping to decipher other genetically complex diseases that have challenged traditional therapeutic approaches. By the end of the year, PCF came to stand for “Precision Cures” Foundation for all human cancer.

Of 9,656 research papers published in 2015, five dominate with research results for patients. Significantly, all of these were funded by PCF and represent a total investment of $9.6 million.

1. Complete Genomic Landscape of Prostate Cancer Mapped

In 2012 PCF provided funding to the East Coast-International Prostate Cancer “Dream Team,” led by Arul Chinnaiyan, MD, PhD (University of Michigan), and Charles Sawyers, MD (Memorial Sloan Kettering Cancer Center), to analyze the genetic profiles of 150 advanced prostate cancer tumors. Despite the enormous scope of this proposed work, the anticipated results promised an unprecedented look at this lethal disease.

Just three short years later, the team unveiled a complete digital image of prostate cancer to the world. Described as the tumor’s genomic landscape, these results identified 17 new molecular targets that may be our best weapon in the fight for permanent remissions. In many ways, these 14 new targets set the entire agenda for the prostate cancer biopharma industry.

This work is highly significant in that it holds the potential to tell doctors precisely who to treat and how they should be treated. Doctors have long recognized that prostate cancer is not a single disease, and that its variations are associated with a wide variety of outcomes. However, with only a microscopes to guide them, there was no way for doctors to match a patient to his optimal treatment. Leveraging recent advances in biotechnology—which permit the relatively rapid and cost-effective characterization of tumors’ genetic profiles—the Dream Team has effectively smashed the “one-size-fits-all” treatment paradigm that has prevailed in the clinic for decades.

This work stands to dramatically improve the care of all prostate cancer patients. The Dream Team’s results mean that if a doctor were to biopsy a tumor, there would be nearly a 90% chance that there would be something actionable—“treatable”—in its DNA. The doctor could then write a precision prescription for the most effective course of treatment, whether FDA-approved or experimental.

2. Resolving Health Disparities in Prostate Cancer: New Signatures Identified

Kosj Yamoah, M.D., Ph.D., Moffitt Cancer Center
Kosj Yamoah, M.D., Ph.D., Moffitt Cancer Center

In 2015, discoveries in prostate cancer genetics helped us better understand the disproportionate disease burden carried by African-American men, who are 70% more likely to develop prostate cancer than any other race or ethnicity, and 2.4 times more likely to die from the disease. A pioneering study by PCF Young Investigator Kosj Yamoah, MD, PhD (Moffitt Cancer Center), identified six new gene biomarker signatures of aggressive disease in African-American men with prostate cancer. These findings, published in the September 1st issue of the Journal of Clinical Oncology, shed much-needed light on the biological factors that predispose African-American men to early, aggressive disease, and provide important targets for future drug development.

This major breakthrough carries with it a new, unanticipated problem: we don’t know the function of most of these genes. In order to address this inequality, we need to get basic science on the function of these genes funded. It is time to invest resources strategically in this arena and solve this disparity for good.

3. Key Mechanism of Metastasis Discovered

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When considering prostate cancer genomics, there is nothing more significant than identifying new vulnerabilities in the disease—targets that can be exploited with new drugs to put patients into lasting remissions. A team of researchers led by Karen Knudsen, PhD (Thomas Jefferson University), has done just that—their studies revealed that a single molecule called DNA-PK drives cancers from being a slow-growing, benign disease into a killer.

Under normal conditions, DNA-PK, along with half a dozen other molecules, helps to combat routine DNA damage. However, Dr. Knudsen’s team, funded in part by the Movember Foundation and the Edward P. Evans Foundation, found that it also helps cancer cells evade many forms of treatment. In men with prostate cancer, they discovered, DNA-PK molecules are recruited by the androgen receptors (AR), which are responsible for feeding male hormones to tumor cells, allowing these mutated cells to survive. By identifying DNA-PK as a key mechanism of metastasis, the team’s research has enormous clinical implications for rationally designed new precision drugs.

4. Treating BRCAness Precisely

In a landmark clinical trial, a new class of cancer drug—originally approved in 2013 for women with rare, inherited forms of breast and ovarian cancer—proved extraordinarily effective in treating men with certain types of chemotherapy- and hormone therapy-resistant prostate cancer. This clinical trial is a major milestone as it is the first study to show the benefit of precision medicine in prostate cancer. The oral drug, olaparib from AstraZeneca, halted tumor growth in 88% of prostate cancer patients with defective BRCA genes, a condition that affects roughly 30% of men with the disease. Even more promising, the drug was also found to benefit many patients who did not harbor BRCA mutations. These exciting findings were published in a PCF-driven report in the New England Journal of Medicine in October. Now PCF is catalyzing a U.K.-U.S. group in partnership with AstraZeneca to do the Phase III trial to secure Breakthrough FDA Designation for olaparib. Plus, we plan to expand R&D on other DNA damage repair drugs, which may work even better than olaparib, in 2016. In North Carolina, one patient with BRCA-mutated prostate cancer, Richard Mackey, reached out to PCF to share his story on how olaparib gave him a new lease on life after all of his other treatment options had been exhausted.

5. Exercise and Healthy Habits Decrease Prostate Cancer Risk

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Even with the most sophisticated analyses, genes alone cannot predict with complete certainty if a man will develop prostate cancer in his lifetime. This is why living a healthy lifestyle is imperative. A new study by Stacey Kenfield, ScD, and June Chan, ScD (University of California, San Francisco), has found that vigorous exercise and other healthy habits may cut a man’s chances of developing lethal prostate cancer by up to 68%. While we have always been aware of the benefits of exercise and nutrition, we now know that they have a direct impact on a man’s prostate health. Not only that, but the same habits that can stave off prostate cancer development and recurrence may also prevent other age-related illnesses including heart disease and diabetes. These findings are especially relevant for older (age 60+) men, men with a family history of prostate cancer, or African-American men, for whom the value of a healthy lifestyle, including a nutritious diet and plenty of exercise, cannot be overstated.

Future Directions

The totality of this work shows, without question, that an investment in PCF means faster and more precise solutions for not just prostate cancer, but for all cancers that claim 580,000 American lives each year. In 2015 we made the fundamental discovery that curing some prostate cancers means cures for 100% of WNT-driven colon cancer patients. BRCA1/1 PALB-driven breast cancer patients will likewise get better drugs from prostate cancer treatment research and development. Soon, all p53 mutant lung cancer patients may get prostate cancer precision medicines. Effective drugs for ETS-driven childhood cancers may come from PCF, and redeployment of prostate cancer precision immunotherapy research biotechnology may treat any form of human malignancy. This means that, in the near future, a physician will be able to biopsy any patient’s tumor and write a precision prescription that matches his exact molecular profile. With these exciting new data, we can say with much certainty that 2015 was a landmark year for the Foundation. It was also completely unlike any other in 113 years of academic urology. With genomic precision we now can see the path to conquering prostate cancer as a fatal disease. We have made seminal progress this year in changing the future of the precision practice of prostate cancer oncology. All this goes to show that after two decades, PCF remains your best investment in a cure.

Terms to know from this article:

Biopsy

The removal of cells or tissues for examination under a microscope. When only a sample of tissue is removed, the procedure is called an incisional biopsy or core biopsy. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. When a sample of tissue or fluid is removed with a needle, the procedure is called a needle biopsy or fine-needle aspiration.

Biomarker

A measurable biological substance that can be used to indicate disease characteristics such as diagnosis, prognosis, or therapeutic responses.

Metastasis

The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a "metastatic tumor" or a "metastasis." The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-ta-seez).

Benign

Not cancerous. Benign tumors do not spread to tissues around them or to other parts of the body.

androgen

A type of hormone that promotes the development and maintenance of male sex characteristics.

Hormone

A chemical made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in a laboratory.

Phase III trial

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

Immunotherapy

Immunotherapy is a type of treatment that boosts or restores the immune system to fight cancer, infections and other diseases. There a several different agents used for immunotherapy; Provenge is one example.

Tumor

A mass of excess tissue that results from abnormal cell division. Tumors perform no useful body function. They may be benign (not cancerous) or malignant (cancerous).

Gene

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

BRCA

Are a human gene and its protein product, respectively. The official symbol (BRCA1, italic for the gene, nonitalic for the protein) and the official name (breast cancer 1).

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