Medical Student Research Fellowship for Summer 2010
Mentor: Sergio Huerta
Room number: A550 VA Medical Center
Phone number: 214-857-0971
Project title: Efficacy of conventional multidrug treatment in radio resistant colorectal cancer HT-29 cells
Human subjects IRB approved project number (where applicable):
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)
Brief Description of Project:
Our laboratory is interested in determining factors that lead to resistance to ionizing radiation in rectal cancer. The clinical problem that we are trying to address is that in most patients treated with the same form of chemoradiation the rate of response is highly variable and unpredictable. For instance, we have treated 117 patients at our institutions with the same form of chemo radiation; there was an observed 24% rate of complete pathological response (cPR). That is, at the time of surgical resection, there was no tumor in the specimen to be identified. However, in the same cohort of patients receiving same form of chemo radiation, 20% of the tumors did not respond to neoadjuvant treatment. There are three aspects of this phenomenon that our laboratory is attempting to understand:
1. What is the phenotype of the radio resistant cells?
2. Are there any predictors that we could use to select patients unlikely to respond to chemo radiation?
3. Are there any radio sensitizing modalities that we can use to shift the group of patients from the radio resistant phenotype to the radiosensitive tumor?
In order to address these issues we have developed in vitro, in vivo, and ex vivo models for the study of the radio resistant properties of tumors. The specific project that Carlos Gonzalez will be involved with during the summer of 2010 will utilize the in vitro model. We have characterized seven colorectal cancer cells in terms of resistance to ionizing radiation. We then identified two cell lines with contrasting phenotypes: the HCT-116 cell line which is exquisitely sensitive to radiation and the HT-29 cell line that is highly radio resistant.
In clinical practice, the response to chemo radiation is highly variable with the use of multiple pre-sensitizing agents. Such pre-sensitizing regimens employ 5-FU, oxaliplatin, irinotecan, bevacizumab, cetuximab either alone or in various combinations.
The main goal of the experimental protocol will be to test all of these agents
in radio resistant HT-29 colorectal cancer cells prior to IR and assess their
growth by clonogenic survival assays. This is a project that will entirely belong
to Carlos, and at the completion of this work, it is likely that the findings
will be both noble and intriguing and that they could potentially lead to a
Previous Research Activities or Publications with Medical Students:
1. Huerta S, Barleben A, Peck MA, Gordon IL. Meckel's Diverticulitis: A Rare Etiology of an Acute Abdomen During Pregnancy. Curr Surg. 2006; 63: 290-293
2. Heinzerling J, Huerta S. Bowel Perforation from Bevacizumab for the Treatment of Metastatic Colon Cancer, Incidence, Presentation and Management. Curr Surg. 2006; 63: 334-337.
3. Heinzerling J, Anthony T, Livingston EH, Huerta S. Predictors of distant metastasis and mortality in patients with stage II colorectal cancer. Am Surg. March 2007; 73: 230-237.Anguiano-Hernandez Y, Chartier A, Huerta S. Smac/DIABLO and Colon Cancer. Anti-Can Agen Med Chem. July 2007; 7: 467-473
4. Barleben A, Huerta S, Mendoza R, Patel CV. Left Ventricle Injury with a Normal Pericardial Window: Case Report and Review of the Literature. J of Trauma. Aug 2007; 63: 414-416.
5. Siddiqui A, Heinzerling J, Livingston EH, Huerta S. Predictors of early mortality in patients with advanced pancreatic cancer. Am J Surg. Sep 2007; 194: 363-367.
6. Huerta S, Heinzerling J, Anguiano-Hernandez Y, Huerta-Yepez S, Lin J, Chen D, Bonavida B, Livingston EH. Modification of gene products in involved in metastatic colon cancer: roles of Fas, Apaf-1, NF B, IAPs, Smac/DIABLO, and AIF. J Surg Res. Sep 2007; 142: 184-194.
7. Chen DJ, Huerta S. Smac mimetics as new cancer therapeutics. Anti-Cancer Drugs. 2009 Sep;20(8):646-58. PubMed PMID: 19550293.
Medical Student in Bold