Modificación de la expresión génica en cáncer de recto tratado con quimio-radioterapia neoadyuvante: papel de trefoil factor 3 como potencial diana terapéutica

Resumen

Introduction: Colorectal carcinoma is one of the leading causes of cancer mortality worldwide, and rectal cancer accounts for 30-35% of these cases Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the current standard of treatment for stages II and III. It improves local control and reduces toxicity and possibly improves disease free survival (DFS) compared with postoperative treatment. However about one third of patients still develop distant metastases and eventually die of the disease. For this reason, current research is focused on prognostic factors to better identify these patients. To date, pathologic TNM stage and circumferential resection margin status are the most important prognostic factors, but changes due to preoperative treatment have to be considered. Tumor regression grade (TRG) as described by Dworak, is assessed by the degree of residual tumor and stromal changes at the site of previous tumor and has been correlated with prognosis. Despite the advances in the knowledge of the multistep process of specific genetic changes that drive the transformation from normal colonic epithelium to an invasive cancer, only KRAS status is currently used in clinical practice for treatment selection in the metastatic setting. The identification of therapeutic targets is crucial to develop alternative strategies to the management of this disease and rectal cancer represents an ideal model for the study of molecular pathogenesis due to the accessibility of tissue for biopsy. In this study we sought to characterize the differential expression by qPCR of selected genes Introduction: Colorectal carcinoma is one of the leading causes of cancer mortality worldwide, and rectal cancer accounts for 30-35% of these cases Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the current standard of treatment for stages II and III. It improves local control and reduces toxicity and possibly improves disease free survival (DFS) compared with postoperative treatment. However about one third of patients still develop distant metastases and eventually die of the disease. For this reason, current research is focused on prognostic factors to better identify these patients. To date, pathologic TNM stage and circumferential resection margin status are the most important prognostic factors, but changes due to preoperative treatment have to be considered. Tumor regression grade (TRG) as described by Dworak, is assessed by the degree of residual tumor and stromal changes at the site of previous tumor and has been correlated with prognosis. Despite the advances in the knowledge of the multistep process of specific genetic changes that drive the transformation from normal colonic epithelium to an invasive cancer, only KRAS status is currently used in clinical practice for treatment selection in the metastatic setting. The identification of therapeutic targets is crucial to develop alternative strategies to the management of this disease and rectal cancer represents an ideal model for the study of molecular pathogenesis due to the accessibility of tissue for biopsy. In this study we sought to characterize the differential expression by qPCR of selected genes