Medical Student Research Fellowship for Summer 2008

Mentor: Sergio Huerta, M.D., F.A.C.S.
Department: Surgery
Room number: E07.126
Mail Code: 9156
Phone number: 214 857-1800
E-mail: Sergio.Huerta@UTsouthwestern.ed
Project title: Factors that lead to radiation resistance in rectal cancer

Human subjects IRB approved project number (where applicable): 052007-035

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Project Type: Basic Science

Brief Description of Project:

In spite of current aggressive multimodality treatments in rectal cancer, recurrence and mortality rates are unacceptably high. Efforts to improve local control and survival in rectal cancer are the focus of multiple current clinical and research efforts. Radiotherapy is currently used as a (neo-) adjuvant modality for rectal carcinoma to aid with surgical intervention or to prevent recurrence, respectively. Pre- intra- or post- operative radiation therapy, however, either alone or in combination with chemotherapy results in a tremendously wide clinical response with nearly 10% of patients achieving complete pathological response and up to nine percent non-responders. Experimental data from my laboratory suggests that in colorectal cancer cells, an increased ratio of anti-apoptotic IAPs (survivin, XIAP) to pro-apoptotic Smac-DIABLO results a radioresistant phenotype. The overall goal of our research protocol is to understand the factors that lead to radiation resistance with the hypothesis the IAP/Smac-DIABLO ratio is affected as indicated by our preliminary studies in vitro. The present protocol will investigate the effects of radiation response based on the expression of XIAP, survivin and Smac-DIABLO ex vivo in rectal cancer tissues patients who underwent surgery for the treatment of rectal cancer. Tissue will be collected from tumors already identified at the Parkland Memorial Hospital (PMH) from archived tissues from patients who underwent surgery for the management of rectal cancer. Tumors will be examined after surgical resection from tissue obtained directly from paraffin-embedded tissue from the tumor to determine the protein levels of survivin, XIAP and Smac-DIABLO by tissue microarray. The medical records of each patient will be interrogated to determine clinical response to radiation treatment as well as the rate of morbidity and mortality. These parameters will be correlated to the levels of expression of survivin, XIAP and Smac-DIABLO.