Abstract B45: Rab5C enhances resistance to ionizing radiation in rectal cancer

Rectal cancer is currently the second most common cancer in the large intestine, and represents one-third of the colorectal cancers that are diagnosed. Neoadjuvant chemoradiation is a well-established protocol for rectal cancer treatment and it reduces the risk of local recurrence. However, a pathologic complete response is only achieved in 10–40% of cases and the mechanisms associated with chemoradiation resistance are poorly understood. To identify potential targets for preventing therapy resistance, a proteomic analysis of biopsy specimens collected from stage II and III rectal adenocarcinoma patients before neoadjuvant treatment was performed. These results were then compared with a proteomic analysis of residual rectal adenocarcinoma tissues that were removed by surgery after neoadjuvant therapy. Three proteins, Ku70, Ku80, and Rab5C, exhibited a significant increase in expression after chemoradiation treatment. To better understand the possible role of these proteins in therapy resistance, a rectal adenocarcinoma cell line was irradiated to generate a radiotherapy-resistant lineage. These cells overexpressed the same three proteins that were identified in the tissue samples. Furthermore, radiotherapy resistance in this in vitro model was found to involve modulation of epidermal growth factor receptor (EGFR) internalization by Rab5C in response to irradiation, and this affected expression of the DNA repair proteins, Ku70 and Ku80. Taken together, these findings indicate that EGFR and Rab5C are potential targets for the sensitization of rectal cancer cells to neoadjuvant treatment and they should be further investigated. Supported by FAPESP - Fundacao de Amparo a Pesquisa do Estado de Sao Paulo. Note: This abstract was not presented at the conference. Citation Format: Antuani Rafael Baptistella, Marcos Vinicios Salles Dias, Fernanda Giudice, Bruna Roz Rodrigues, Petrus Paulo Combas Eufrazio Silva, Edson Kuatelela Cassinela, Tonielli Lacerda, Fabio Marchi, Adriana Franco Paes Leme, Maria Dirlei Begnami, Samuel Aguiar Junior, Vilma Regina Martins. Rab5C enhances resistance to ionizing radiation in rectal cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; Sao Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B45.