Apoptosis in cancer cell signaling and current therapeutic possibilities

Abstract

Apoptosis is programmed cell death, which sustains the equilibrium between survival and death in eukaryotic cells. It is a tightly regulated cell death program that aims at eliminating harmful, damaged, or unwanted cells. This wisely programmed cell death is central in the development of all multicellular organisms, which is highlighted by the prevalence of diseases associated with abnormal apoptosis. For example, defect in apoptosis is a hallmark of cancer, whereas excessive cell death occurs in several neurodegenerative disorders. The cell death signals are responsible for maintenance of the genomic integrity, while defective cell death may stimulate carcinogenesis. These signals are convoluted and are controlled at various points. Tumor cells survive by taking help of several different molecular mechanisms to inhibit apoptosis and acquire resistance to apoptotic agents, for example, by the expression of anti-apoptotic proteins such as Bcl-2 or by the downregulation or mutation of pro-apoptotic proteins such as BAX. This chapter includes recent developments in the field and reviews new evidences of the interconnection between apoptosis and cancer. Various molecules that can be regulated to facilitate apoptosis in myriad of cancers are also enlisted. Overall, the chapter discusses about the development of various treatments and approaches to combat cancer by targeting anti-apoptotic proteins belonging to Bcl-2 and IAP families.