Mol Cancer Res: a new target for colon cancer treatment

February 15, 2020 / Biovalley / -- researchers have found a way to help chemotherapy treat colon cancer more effectively They found a new pathway (rictor / mtorc2) that is a biological target for colon cancer Targeted inhibition of rictor or mtorc2 pathway may be a unique treatment for colorectal cancer chemotherapy "Finding biomarkers that enhance the sensitivity of cancer cells to chemotherapeutic drugs has become a priority for effective treatment of cancer, and it is to reduce the toxicity caused by chemotherapy or to overcome the new hope of drug resistance," explained Dr Sam thiagalingam, co-author of the study, biomedical genetics at the Boston University School of Medicine (BUSM) Associate professor of science, medicine, pathology and experimental medicine, as well as pharmacology and experimental therapeutics Source: NIH thiagalingam and his colleagues have previously found that Smad4 gene mutation is related to advanced colon cancer, and Smad4 acts as a transfer inhibitor by blocking the function of transcription factors that promote the progression of metastatic cancer through interaction In addition, clinical data and studies conducted by thiagalingam et al Using a cell culture system have found that the loss or low expression of Smad4 is related to the adverse reactions of 5-fluorouracil, which is the basis of almost all chemotherapy combinations used for the treatment of metastatic colon cancer The researchers speculate that Smad4 can not only block the function of transcription factors, but also promote the function of transfer signal pathway, so as to induce the function of transfer inhibitory factors "For the first time, we found that Smad4 interacts with rictor to inhibit the function of mtorc2, so the loss of Smad4 function leads to the carcinogenic activation of mtorc2 pathway, the enhancement of metastatic colon cancer progression and the resistance to chemotherapy drugs," thiagalingam said "According to the researchers, this study shows that cancer treatment based on chemotherapy drugs such as irinotecan combined with drugs targeted at inhibiting rictor / mtorc2 pathway will be very effective for colon cancer, pancreatic cancer or other cancers that cause Smad4 dysfunction In addition to colon cancer, Smad4 mutations, deletions and low levels in glioma, pancreatic cancer, prostate cancer and lung cancer are also associated with poor prognosis The findings are published online in the Journal of the American Cancer Research Association, molecular cancer research Reference: Sam thiagalingam et al Targeting rictors sensitises Smad4 negative colon cancer to irinotec Molecular cancer research 2020.doi: 10.1158/1541-7786.mcr-19-0525