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Colorectal cancer (CRC) is the second most common malignant neoplasm in women and the third most prevalent in men worldwide. In Brazil, about 36,000 new cases of CRC are estimated among men and women for 2018-2019. With advances in treatment, early CRC is being “reclassified” from a deadly disease to an illness that has great chance of cure. However, so far, the survivors who have completed treatment and are cancer-free, frequently suffer from late/longterm side effects, and some patients with metastasis have poor response to the therapies. In this context, the discovery of new therapeutic strategies is urgently needed. In this project we aimed to validate the hypothesis that 3Bromopyruvate (3-BP), an alkylating agent, would be able to sensitize the human CRC cell lines to treatment with Vemurafenib, a BRAF inhibitor. Therefore, human CRC cell lines (HT-29 and HCT-116) were challenged with 3-BP followed by the treatment with Vemurafenib. Both cell lines were more responsive to Vemurafenib after sensitization with 3-BP (IC50 values were 7and 1.4-fold lower than with Vemurafenib alone, for HT-29 and HCT-116 cells, respectively). The findings presented here, highlight the potential of 3-BP in increasing the response of metastatic cancer cells to Vemurafenib.

Human colorectal cancer cells become more responsive to Vemurafenib after sensitization with 3-Bromopyruvate