Therapeutic Exploitation of Targeting Programmed Cell Death for Cervical Cancer

Cervical cancer is the most prevalent malignancy of the female reproductive system. Several randomized controlled studies have shown survival benefits of platinum-based neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer. Survival benefit of neoadjuvant chemotherapy depends on high chemoresponsiveness. Considerable evidence indicates that platinum can kill cells through the induction of apoptosis; however, cancer cells, in their relentless drive to survive, hijack cell processes, resulting in resistance to apoptosis. This resistance underlies not only tumorigenesis, but also the inherent resistance of certain cancers to chemotherapy and radiotherapy. Fortunately, in addition to inducing apoptosis, a number of chemotherapeutic agents have been shown to induce nonapoptotic forms of cell death. The significance of nonapoptotic cell death in chemotherapy, and the mechanisms by which it is induced remain less well understood. Given the fact that most cancer cells have defects in the response to induction of apoptosis, it would be desirable if therapeutic agents could kill cancer cells resistant to apoptosis through alternative mechanisms.