New Trials to Beat Cancer
words by mary ann littell /
photograph by pete byron
he good news for cancer patients is that there has been a significant improvement in their rate of survival over recent years,” says Robert S. DiPaola, MD. “We attribute that in part to successful research — not only in therapeutics, but also in screening, and our ability to catch cancers at an earlier stage.”
DiPaola, a noted prostate cancer researcher, was named director of CINJ in September 2008. He also oversees its prostate cancer program and has continued his involvement in research. “As we gain knowledge about what makes cells become cancerous, we’re able to identify new targets for medicines and translate these targeted agents into clinical trials,” he says.
Prostate cancer is the second leading cause of cancer death in men, and one in six men will be diagnosed with it in his lifetime. DiPaola oversees a number of clinical trials for prostate cancer with the help of a team that includes faculty members Mark Stein, MD, Isaac Kim, MD, Sung Kim, MD, Mary Todd, DO, Robert Weiss, MD, and Biren Saraiya, MD. He recently completed a national trial evaluating the effectiveness of a prostate cancer vaccine developed at CINJ. It is administered to patients with prostate cancer to prevent recurrence. The physician says, “We’re answering two questions: Did it benefit the patients by decreasing their PSA as a marker for tumor progression? And did it produce an immune response to prostate cancer?” He presented the results of the trial at the annual meeting of the American Society of Clinical Oncology in February showing an effect of the vaccine on PSA.
Another area of cancer research showing great promise is the use of anti-angiogenic drugs, which block blood vessel formation, essentially starving tumors. DiPaola explains that’s easier said than done. “Cancer cells are tough to kill,” he says. “When targeted with anti-angiogenic agents, they undergo a metabolic shift called autophagy. It’s a potential survival mechanism whereby the cell consumes its own internal organelles — gets rid of its own excess baggage, so to speak. It becomes trimmer and leaner, needs less energy and is resistant to therapy.” Laboratory studies by DiPaola, Eileen White, Shengkan Jin and Vassiliki Karantza-Wadsworth at CINJ have shown that many of the agents currently used to treat cancer will induce this process, which may allow the cells to live much longer.
At CINJ, a multidisciplinary group of laboratory and clinical investigators dubbed the Autophagy Team meets regularly to study this process. “The goal is to understand how this discovery can be used to improve current therapies,” says DiPaola. A series of three Phase II clinical trials have resulted from this collaboration, targeting breast, lung and prostate cancer. “These trials, which are specific to CINJ, will evaluate whether giving the drug hydroxychloroquine along with standard chemotherapy will inhibit autophagy.”
CINJ is also working with the National Cancer Institute’s (NCI) Cancer Therapy Evaluation Program (CTEP) to develop effective therapies for cancer. CTEP funds a national program of cancer research and sponsors clinical trials to evaluate new anti-cancer agents. CINJ is one of a handful of cancer centers nationally to have a UO1 grant with the NCI to fund the development of new agents. “It’s a privilege to be part of this exceptional program, which provides us with another opportunity to evaluate very novel agents,” explains DiPaola. “Having such a diverse menu gives us many clinical trial options to offer patients who are in need of new therapies.”