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Scientists take fight against prostate cancer from lab to clinic

deKernion
Dr. Jean deKernion is a pioneer in the field of prostate cancer research at UCLA.
The awarding of $11.6 million in federal funding from the National Cancer Institute (NCI) to enable a multidisciplinary group of UCLA scientists to continue their important prostate cancer research is just the latest in a string of "big hits" for the team.
 
"To get something like this funded now is really something," said Dr. Jean deKernion, professor emeritus who pioneered prostate cancer research at UCLA two decades ago and was one of the first principal investigators when UCLA’s Specialized Program of Research Excellence (SPORE) site in prostate cancer  started in 2001.
 
This award marks the third round of NCI funding for the SPORE group, which is comprised of UCLA scientists, clinicians, oncologists, radiologists, pathologists and imaging specialists. Together, they’ve turned UCLA into one of the nation’s preeminent research engines for advances in the prevention, diagnosis and treatment of prostate cancer and made a life-saving difference in the lives of countless patients and their families.
 
"This renewal of the UCLA prostate SPORE is indicative of the world-class research we have on this campus," said Dr. James Economou, UCLA vice chancellor for research and professor of microbiology, immunology and molecular genetics; molecular and medical pharmacology; and surgical oncology.
 
Roughly one in six men will be diagnosed with prostate cancer, making it the second most common cancer in men. It is estimated that 238,000 new cases of prostate cancer will be diagnosed in the United States this year, and about 30,000 men will die from the disease.
 
The SPORE program has been key in advancing preventative care and developing diagnostic tools and therapies.
 
"UCLA's world-class research in prostate cancer, joined with over 15 years of faculty entrepreneurial initiative and technology transfer efforts, are bringing life-saving technology to the clinic and the marketplace," said Emily Loughran, director of licensing in UCLA’s Office of Intellectual Property and Industry Sponsored Research. "It is truly gratifying to see a lot of hard work come to fruition."
 
Jung
Dr. Michael Jung has been behind the creation of two valuable compounds that aid in the fight against prostate cancer.
From lab to clinic
 
In June, Johnson & Johnson, a manufacturer of multinational medical devices and pharmaceutical and consumer packaged goods, struck a $1 billion deal with Aragon Pharmaceuticals Inc., a UCLA start-up and leader in developing drugs that fight hormone-driven cancers, to acquire the rights to a UCLA-developed androgen receptor antagonist program. This program includes ARN-509, a second-generation androgen receptor-signaling inhibitor designed and synthesized in 2006 by a UCLA team headed by former SPORE investigator Dr. Charles Sawyers, who worked at the Jonsson Comprehensive Cancer Center for nearly 18 years, and Dr. Michael Jung, a professor of chemistry and biochemistry. This compound is currently being evaluated in multiple Phase II trials in men with castration-resistant prostate cancer.
 
In addition, the UCLA-created prostate cancer drug Xtandi, a new anti-androgen treatment that can prolong life for men who have failed hormone and chemotherapies, received approval from the U.S. Food and Drug Administration in 2012. Xtandi, which was also developed by Sawyers and Jung and later licensed to California’s Medivation Inc., inhibits the androgen receptor (AR), the engine of prostate cancer progression, at three distinct points in the signaling pathway. In its Phase III clinical study, Xtandi increased median survival by 4.8 months in men with the chemotherapy-resistant disease, providing a 37 percent reduction in the risk of death compared to placebo.
 
"These two drugs are effective in the large number of patients with advanced prostate cancer who were previously not treatable," said deKernion, who continues to practice medicine at the Frank Clark Urology Center at the Ronald Reagan UCLA Medical Center. "That’s quite an accomplishment."
 
Currently, SPORE researchers are working on a variety of other projects, including new clinical trials; studies related to the role of diet, such as the impact of fat and fish oil consumption on prostate cancer; new imaging methods that are expected to result in more effective ways to detect, target and treat the disease; and the development of personalized therapies for men with resistant prostate cancer.
 
Rob Reiter
Dr. Robert Reiter co-founded two spin-off companies to bring UCLA therapies to the public market. The most recent, ImaginAB, was co-founded with Dr. Anna Wu.
Research results in a trio of spin-offs
 
The SPORE team has also experienced unmatched success with the creation of spin-off companies that apply scientific discoveries to help improve and extend the lives of prostate cancer patients.
 
In addition to Aragon, the company that inked the deal with Johnson & Johnson, SPORE researchers have been behind Agensys, which took flight in 1998 after its seven co-founders licensed from UCLA the prostate stem cell antigen (PSCA) gene and antibody developed by co-founders Dr. Robert Reiter, SPORE director and principle investigator, Bing Professor of Urologic Research and a member of the Jonsson Cancer Center; and Dr. Owen Witte, director of the Broad Stem Cell Research Center and professor of microbiology; and a prostate-specific promoter technology invented by Dr. Arie Belldegrun, also a co-founder and now director of UCLA's Institute of Urologic Oncology. The company, which focused on the development of cancer antibodies, was sold to Astellas in 2007.
 
Anna Wu l
Dr. Anna Wu and Dr. Reiter are currently working to bring N-cadherin-targeted antibody therapy into the clinic.
The other is ImaginAB, founded by Reiter and Dr. Anna Wu, professor and vice chair in the department of molecular and medical pharmacology at the David Geffen School of Medicine. One of their first licensed inventions was antibody fragments that target the prostate stem cell antigen. These are entering the clinic this month, said Reiter.
 
"Few, if any, programs have led to as many spin-off and commercial licenses," Reiter said.
 
The early years
 
The impact UCLA has had in this field of medicine has been incredibly valuable, said deKernion, adding that he started his prostate cancer research cluster 20 years ago when there was very little funding available.
 
"In the mid-90s, UCLA was a big center for prostate cancer therapy," said deKernion. "Some clinical progress in prostate cancer treatment had been made here years before, but like almost everywhere else in the country, there just wasn’t enough research related to prostate or any other urologic cancers to speak of, except for clinical trials."
 
In addition, surgery, often involving castration, was quite crude, radiation therapy had a host of negative side effects and hormone therapies were limited.
 
"Once standard therapies failed, further options were not available," deKernion said.
 
To garner more financial support for the valuable work being done here in the 90s and for future efforts to better prevent, diagnose and treat this silent killer, deKernion decided to expand his kidney cancer work to include prostate cancer research.
 
Witte 2
Dr. Owen Witte and his colleagues are researching prostate cancer stem cells, which are thought to be resistant to castration and most conventional therapies. This project will focus on targeting a gene called Trop-2, which is present on normal and malignant prostate stem cells.
To do so, deKernion enlisted Witte to help found UCLA’s prostate cancer research program. DeKernion and Witte then added Reiter and Sawyers, both of whom had completed postdoctoral training with Witte, to their group. The program gained momentum between 1995 and 2001 with the recruitment of several on- and off-campus investigators and securing initial funding, including their first multimillion dollar grant from NCI in 2002.
 
"My concept was that the thoughtful clinicians that were interested and understood the problems that needed to be dealt with and the discoveries that had to be made, needed to work side by side with basic scientists committed to solving those problems," he said.
 
"Today, I can say that survival rate for patients is better, treatment is less toxic, and we know more and more about who should be treated and who shouldn’t. There is no doubt in my mind that we are leagues better than we were back then, and I don’t think anybody would argue with that."