Targeting cell death: a promising approach for colorectal cancer therapy

Colorectal cancer is one of the most common digestive malignancies worldwide. Cell death plays a crucial role in maintaining normal biological functions and homeostasis, with dysregulation of cell death leading to tumorigenesis. In addition to apoptosis, necroptosis, pyroptosis and ferroptosis, it is PANoptosis, cuproptosis and disulfidptosis that are involved in the development of CRC. Radiotherapy, chemotherapy, targeted therapy and immunotherapy are the main treatments for advanced CRC. These therapies induce CRC cell death through various pathways, including increased intracellular ROS, induced DNA damage, inhibiting the specific signaling pathways and activating the immune system. Cell death can regulate CRC cells’ sensitivity to treatment through complex mechanisms, suggesting that targeting cell death could not only inhibit rapid CRC cell proliferation but also overcome treatment resistance. This review summarizes the current understanding of various CRC mechanisms and the primary mechanisms by which existing CRC treatments induce cell death. Additionally, we highlight recent research advancements in targeting cell death for CRC treatment and describe numerous challenges encountered in clinical practice. Aiming to provide effective strategies and new perspectives for CRC treatment and to lay a solid theoretical foundation for the development of drugs targeting CRC cell death.