Abstract 598: Characterization of biological activity in colorectal cancer cells to anticancer regimens

There have been significant advances in the use of chemotherapy in the treatment of colorectal cancer (CRC) patients over the last 20 years. A goal of cancer therapy is to predict patient response and toxicity to drugs in order to facilitate the individualization of patient treatment. Identification of subgroups of patients that differ in their prognosis and response to treatment could help to identify the best available chemotherapy according the biological activity. In metastatic CRC, novel molecular targeted agents are being developed as the pathways that characterize cell growth, the cell cycle, apoptosis, angiogenensis and invasion provide novel targets for cancer therapy. The purpose of this study was to evaluate the efficacy of monotherapy and combination chemotherapy with targeted drugs in the CRC cell death pathway. The chemosensitivities of 12 CRC cell lines to established regimens [FX (5-FU + leucovorin + oxaliplatin) and FR (5-FU + leucovorin + irinotecan)], two biologically targeted drugs (bevacizumab + cetuximab) were comparatively evaluated through various cell death pathways; apoptosis, angiogenesis, invasion and autophagy. In this study, the cell deaths by apoptosis and invasion were associated with the respective chemotherapeutic regimens. Monotherapy using bevacizumab and cetuximab did not induce significant tumor inhibition, but treatment with combination of FX and FR led to significantly higher response rates than those to FX and FR alone. SW480 cell was expressed significantly higher apoptotic cell death and activasion of caspase-3 to the all drugs. Additionally, the MMP-9 activity remarkably reduced in the drug-treated SW480 cell compared with other cells. The SW480 cell shows the microsatellite-stable, functionally p53-deficient, hMLH1-proficient and kras mutation. These molecular and genentic profiling were associated with the chemosensitivity of SW480 cell to respective regimens. In future studies, it will important to combine these genetic profiling with the various CRC cancer cell death pathways to identify the tumor response to chemotherapy and finally realize an individualized treatment regimen to each patient. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 598. doi:10.1158/1538-7445.AM2011-598