Rational targeting of autophagy in colorectal cancer therapy: From molecular interactions to pharmacological compounds

The abnormal progression of tumors has been a problem for treatment of cancer and therapeutic should be directed towards targeting main mechanisms involved in tumorigenesis in tumors. The genomic mutations can result in changes in biological mechanisms in human cancers. Colorectal cancer is one of the most malignant tumors of gastrointestinal tract and its treatment has been faced some difficulties due to development of resistance in tumor cells and also, their malignant behavior. Hence, new therapeutic modalities for colorectal cancer are being investigated. Autophagy is a self-digestion mechanism that is responsible for homeostasis preserving in cells and its aberrant activation/inhibition can lead to tumorigenesis. The current review focuses on the role of autophagy mechanism in colorectal cancer. Autophagy may be associated with increase/decrease in progression of colorectal cancer due to mutual function of this molecular mechanism. Pro-survival autophagy inhibits apoptosis to increase proliferation and survival rate of colorectal tumor cells and it is also involved in cancer metastasis maybe due to EMT induction. In contrast, pro-death autophagy decreases growth and invasion of colorectal tumor cells. The status of autophagy (upregulation and down-regulation) is a determining factor for therapy response in colorectal tumor cells. Therefore, targeting autophagy can increase sensitivity of colorectal tumor cells to chemotherapy and radiotherapy. Interestingly, nanoparticles can be employed for targeting autophagy in cancer therapy and they can both induce/suppress autophagy in tumor cells. Furthermore, autophagy modulators can be embedded in nanostructures in improving tumor suppression and providing cancer immunotherapy.

Automated summary

The abnormal progression of tumors has been a problem for cancer treatment, and therapy should target the main mechanisms involved in tumorigenesis. Genomic mutations can lead to changes in biological mechanisms in human cancers. Colorectal cancer, a highly malignant gastrointestinal tumor, poses challenges due to tumor cell resistance and aggressive behavior. New therapeutic methods for colorectal cancer are being explored, with a focus on the role of autophagy. Autophagy plays a dual role in the progression of colorectal cancer, with pro-survival autophagy promoting cell proliferation and survival, while pro-death autophagy inhibits tumor growth and invasion. The modulation of autophagy status is crucial for therapy response, and targeting autophagy can enhance the sensitivity of colorectal tumor cells to chemotherapy and radiotherapy. Nanoparticles show promise in targeting autophagy for cancer therapy, and autophagy modulators embedded in nanostructures may improve tumor suppression and facilitate cancer immunotherapy.