University of Pittsburgh Medical Center Cancer Centers and Cancer Institute
By Wayne Kuznar
The University of Pittsburgh Medical Center (UPMC) Cancer Centers work in tandem with the University of Pittsburgh Cancer Institute (UPCI) to offer advances in cancer prevention, early detection, diagnosis, and treatment throughout a three-state region (western Pennsylvania, Ohio, West Virginia). UPCI has been designated as a Comprehensive Cancer Center by the National Cancer Institute (NCI). UPCI ranked 11th in funding from the NCI in 2007, and 12th among U.S. News & World Report's "Best of the Best" cancer programs in the nation.
UPMC's network of 2300 physicians, scientists, staff, and other healthcare professionals provides clinical care to 30,000 patients annually at its facilities while engaging in cutting-edge cancer re - search. Medical, radiation, and surgical oncologists and disease-specific specialists collaborate closely in a model of multidisciplinary care. Ancillary service providers in behavioral medicine, rehabilitation, social work, palliative care, nutrition, and genetic counseling are incorporated into the multidisciplinary team to ensure that all aspects of care are addressed.
The hub and satellite network of UPMC Cancer Centers consists of more than 45 community-based locations in western Pennsylvania and two centers in Ireland.
The hub-and-spoke model ensures extensive distribution of radiation therapy and medical oncology facilities throughout the tri-state region, said Barry Lembersky, MD, a medical oncologist. "Our pathways of standard of care are uniform throughout this area, and the full array of clinical trials is available to patients at all satellite facilities," he said.
Thirteen areas of expertise
The range of knowledge covers virtually all types of adult cancer, with 13 areas of expertise being recognized, including a world-renowned melanoma program. Other programs are devoted to brain cancers, breast cancer, colon and gastrointestinal cancers, head and neck cancers, leukemias and lymphomas, liver cancer, lung cancer, gynecologic cancers, prostate and urologic cancers, and stemcell transplantation.
The Melanoma and Skin Cancer Program consists of both basic and clinical research and has patients coming from all over the world to participate in clinical trials for melanoma under the direction of John Kirkwood, MD. Major areas of research range from the development of a melanoma vaccine to the search for biomarkers to aid in the development of personalized treatments. UPMC was one of the first centers to use a digital mole mapping system to assess high-risk patients for skin cancer.
In addition, UPMC has "a well-organized pancreatic cancer program whereby patients with all forms of pancreatic cancer and all stages are seen in a multidisciplinary clinic with innovative clinical trials in the preoperative setting and the adjuvant and metastatic setting," Lembersky said.
For instance, a preoperative clinical trial of gemcitabine with radiation therapy and bevacizumab is in progress, with the goal of evaluating the downstaging and histologic changes that occur with such treatment. "That's a pretty novel approach that holds promise not only for better outcome but for the paradigm of evaluating new drugs and new drug combinations; give the drugs prior to pancreatic resection to look for surrogate markers of response (ie, tumor necrosis), and correlate it with long-term outcome," he said. "The treatment has been very well tolerated and resection rates are high. In most patients, there is evidence of significant necrosis and chemotherapy or radiation effect, and what that means for survivorship is uncertain at this time."
Other research involves the testing of a vaccine for colon cancer prevention in persons at high risk for developing the disease. In a novel approach, the vaccine is directed against an abnormal variant of the gene MUC1, which is altered and produced in excess in advanced adenomas and cancer. Stimulating an immune response against the protein encoded by MUC1 in precancerous growths may not only trigger the immune system to destroy the abnormal cells to prevent progression to cancer but may also prevent polyp recurrence. MUC1 vaccines have been tested for safety and immunogenicity in patients with late-stage colon cancer and pancreatic cancer.
Integrated drug discovery program allows for range of studies
A vertically integrated drug development program at UPCI, called Molecular Therapeutics Drug Discovery, employs 69 members with interests in one of four areas: chemical diversity, molecular targets, pharmacokinetics/ pharmacodynamics, and phase 1 clinical trials. "The goal is to have seamless movement from chemistry into patients, and if we make observations in patients, to be able to take them back and look at them on a mechanistic/molecular level," said Merrill Egorin, MD, professor of medicine at UPCI.
"We are one of the six NCI animal pharmacology contractors, so that puts us in the pipeline of any drug that the NCI is considering putting into patients," he said. "We've got an early signal on what's coming through the NCI. If we have inplace methods to measure the drug—we've defined its metabolism, we know its molecular targets, and we have assays to measure those molecular targets in animal models of tumors—it's a huge strength when we put in a request to do a first-in-human study or phase 2 study," Egorin said.
Researchers at UPCI are also involved in a number of ongoing studies with the target poly (ADP-ribose) polymerase (PARP), an enzyme involved in the recognition of DNA damage and repair. By inhibiting PARP, the hope is that the activity of anticancer drugs can be potentiated, presumably by decreasing the resistance or increasing the sensitivity of tumor cells to standard chemotherapy.
BRCA1- and BRCA2-mutated tumors should be specifically sensitive to inhibition of PARP, according to Egorin. This synthetic lethal approach has already been validated in vitro and in preclinical models. "There has already been a clinical study with a different PARP inhibitor that has demonstrated the case that BRCA tumors will respond to this, and the toxicities are essentially none," he said.
