Pancreatic cancer (PDAC) is the fourth leading cause of cancer-related deaths in the United States, with an overall five-year survival rate of less than five percent. Most patients (85 percent) present with locally advanced or metastatic disease and are not candidates for surgery. Even those patients who undergo surgery have a five-year survival rate of less than 20 percent. Unresectable patients have a median survival of less than 12 months, with current Gemcitabine-based chemotherapeutic regimens extending survival only by a median of five weeks. The poor outcome of patients with PDAC has been attributed to the advanced stage of disease at diagnosis, the poor response to systemic and local therapies, and the aggressive biological nature of the disease. Thus better strategies for earlier detection and treatment are needed.
Dr. Timothy Donahue researches the molecular signature of PDAC that is responsible for PDAC initiation and progression, with an overall goal of using these gene/expression changes as markers of earlier detection and/or targets for therapy. To aid in their investigation, Donahue and his colleagues have developed a number of unique transgenic mouse models that reliably recapitulate human PDAC with well-defined kinetics. UCLA is a high-volume pancreatic surgery center, with more than 100 pancreatic resections performed annually for PDAC. Thus, they are able to translate their pre-clinical findings to patients in a high-throughput manner. Donahue envisions a pancreatic cancer program at UCLA whereby individual patient tumors are molecularly profiled to select the most effective targeted agents for that patient.
Selected Cancer-Related Publications:
Ribas A, Comin-Anduix B, Economou JS, Donahue TR, de la Rocha P, Morris LF, Jalil J, Dissette VB, Shintaku IP, Glaspy JA, Gomez-Navarro J, Cochran AJ. Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade. Clin Cancer Res. 2009 Jan 1;15(1):390-9.
Donahue TR, Hines OJ. CXCR2 and RET single nucleotide polymorphisms in pancreatic cancer. World J Surg. 2009 Apr;33(4):710-5.
Vo DD, Prins RM, Begley JL, Donahue TR, Morris LF, Bruhn KW, de la Rocha P, Yang MY, Mok S, Garban HJ, Craft N, Economou JS, Marincola FM, Wang E, Ribas A. Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824. Cancer Res. 2009 Nov 15;69(22):8693-9. doi: 10.1158/0008-5472.CAN-09-1456. Epub 2009 Oct 27.
Donahue TR, Hiatt JR, Busuttil RW. Collagenase and surgical disease. ernia. 2006 Dec;10(6):478-85.
Di Sciullo G, Donahue T, Schachner M, Bogen SA. L1 antibodies block lymph node fibroblastic reticular matrix remodeling in vivo. J Exp Med. 1998 Jun 15;187(12):1953-63.