NEW YORK, NY (January 17, 2018)–The Lustgarten Foundation has awarded Columbia University's Herbert Irving Comprehensive Cancer Center (HICCC) a three-year grant, as part of its Translational Clinical Program, to test a new precision medicine approach to the treatment of metastatic pancreatic cancer.
"The prevailing model in personalized cancer treatment is to attack the DNA mutations that are believed to be driving an individual patient's tumor," says principal investigator Kenneth P. Olive, PhD, assistant professor of medicine and pathology & cell biology at HICCC. "While this approach has been astonishingly effective for a handful of rare cancers, we expect it will only work for a very small fraction of patients with the most common types of cancer."
Pancreatic ductal carcinoma (PDA)–the most common form of pancreatic cancer–is a case in point. Researchers have identified few genetic drivers in pancreatic tumors, and the most common driver (KRAS) is not easily targeted. Conservatively, only about 15 percent of PDA patients are likely to benefit from conventional DNA mutation-based precision medicine therapies and most of these will either not respond or will relapse with a drug-resistant form of the disease.
"Our study takes an entirely new approach," says Dr. Olive. "Instead of looking at the mutations encoded in a tumor's DNA, we analyze the tumor's RNA. Since RNA is the tissue-specific 'working copy' of a cancer cell's DNA, it's a more accurate reflection of the genetic programs that are active in a tumor and critical for its survival. We can then match the patient to approved and investigational drugs that inhibit those programs."
The approach for matching patients to drugs based on their tumor RNA was developed by Andrea Califano, Dr, Chair of the Department of Systems Biology and a co-leader of the grant. In preliminary tests of this approach–called OncoTreat–on PDA tumor samples, the researchers identified at least one matching drug for 85 percent of patients. The approach has also been tested on other cancers and is the first NYS Department of Health CLIA approved RNA-based test to match patients to the full repertoire of FDA-approved and investigational drugs in phase 2 and phase 3 clinical trials. To date, three of four patients who received OncoTreat therapy have exhibited clinical responses.
"OncoTreat identifies drugs that can invert the activity of a novel class of cryptic cancer targets, called master regulator proteins," says Dr. Califano. "These proteins, which are conserved within large subsets of cancer patients and represent the 'engine room' of the cancer cell, are responsible for integrating the effect of individual genomic alterations and for making the cancer cell impervious to a wide range of perturbations, including those resulting from conventional drug treatment. By targeting the 'engine room' of the cancer cell, we hope to develop more universal and more effective treatment."
The primary goal of this phase 1b clinical trial is to assess anti-cancer activity of OncoTreat-predicted drugs in 30 patients with recurrent PDA, on an individual patient basis. The grant will also support preclinical studies to develop optimized two-drug regimens for groups of PDA patients based on their OncoTreat profile. The program comprises a multidisciplinary team of clinicians, experimental biologists, and computational biologists working in close collaboration to deploy an entirely new approach to precision medicine in pancreatic cancer.
"PDA is a highly lethal disease with no truly effective treatment options," says Dr. Olive. "New approaches to this disease are desperately needed."
The Lustgarten Foundation, based in Woodbury, NY, is a leading private foundation dedicated to funding pancreatic cancer research.
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Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.
The Herbert Irving Comprehensive Cancer Center (HICCC) of Columbia University (CU) is the University's organizational structure for the conduct of basic, clinical and population-based cancer research and patient care. Cancer Center researchers and physicians are dedicated to understanding the biology of cancer and to applying that knowledge to the design of cancer therapies and prevention strategies that reduce its incidence and progression and improve the quality of the lives of those affected by cancer.
Columbia's interest in cancer research dates from 1911 with the creation of the Institute for Cancer Research. Initially funded by the National Cancer Institute (NCI) in 1972 and designated comprehensive in 1979, the HICCC is one of only 49 NCI-designated comprehensive cancer centers in the United States, of which only three are in New York State.
Today, the HICCC has more than 280 members from seven schools at Columbia University. Eight research programs are organized into three divisions – basic, disease-specific, and population-based science. The Center also supports and manages 17 shared resources which provide services that are essential to cancer research.
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