Reactivating apoptotic pathways in cancer: A review of novel therapeutic approaches

Apoptosis is a fundamental biological process that eliminates damaged or undesired cells in a controlled way, maintaining cellular equilibrium. A family of cysteine proteases called caspases is responsible for controlling this highly regulated type of cell death. Under typical physiological circumstances, apoptosis keeps damaged cells from building up and preserves tissue integrity. However, genetic alterations, overexpression of anti-apoptotic proteins, and downregulation of pro-apoptotic factors provide cancerous cells the capacity to resist apoptosis. Tumor cells can multiply unchecked, disturb cellular homeostasis, and become resistant to traditional treatments because of their resistance to regulated cell death (RCD). Using targeted therapies to induce apoptosis is one of the potential ways to combat this. On the other hand, cancers frequently have death pathway plasticity, which enables them to alternate between cell death processes in response to therapeutic pressure. This review goes beyond apoptosis to examine other mechanisms of RCD, such as ferroptosis, necroptosis, and autophagy, as well as the signaling networks that link them. The review focusses on tumor microenvironmental elements, including oxidative stress, hypoxia, immunological regulation, and metabolic cues, affect the dynamics of cell death and the treatment results. It is crucial to comprehend the interactions between apoptosis and non-apoptotic processes to create more effective combination methods that can get beyond resistance. This review's insights provide a strong foundation for developing adaptive, targeted strategies that overcome resistance by leveraging crosstalk between regulated cell death pathways.