Apoptosis (called as programmed cell death) is vital for maintaining
homeostatic balance between cell survival/cell deaths in metazoan cells. Apoptosis is
regulated through extrinsic (or receptor mediated) and intrinsic (or mitochondria
mediated) pathways. The pro-apoptotic proteins (e.g. Bax, Bak, Bad, Bcl-Xs, Bid, Bik,
Bim and Hrk) and the anti-apoptotic proteins (e.g. Bcl-2, Bcl-XL, Bcl-W, Bfl-1 and
Mcl-1) are crucial to control the apoptotic pathways. Dysfunctions of apoptosis
pathways are implicated in cancer as defects in these pathways not only promote
tumorigenesis but also confer resistance to cancer cells to most conventional
chemotherapies as well as radiotherapy. The apoptosis occurs by imbalanced proapoptotic
and anti-apoptotic protein levels, impaired or reduced death receptor
signalling and caspase function. Hence, targeting apoptosis pathways is considered as
an attractive strategy for therapeutic intervention in cancer. The past decade recorded
tremendous advances in this area especially small molecular intervention of apoptosis
pathways for cancer treatment which resulted in several compounds under clinical
development. This chapter reviews the current progressions in the development of
bioactive molecules targeting apoptotic pathways with special emphasis on small
molecular anticancer drugs under clinical trials. Some excellent examples are; nutlins,
MI-888, MI-219 and SM-164 which target MDM2, ABT-263, AT-406 and GX15-
070MS which target Bcl-2 family of proteins, birinapant, GDC-0917, HGS-1029 and
LCL-161 which target IAPs (inhibitors of apoptotic proteins). The content of this
chapter will be enlightening the readers in academic and research to update their
knowledge on the anticancer drugs especially target proteins responsible for apoptosis.
Keywords: Apoptosis, BCL family proteins, Cancer, Caspase, Clinical trials,
IAP, MDM2, Nutlins, p53, Pro-apoptotic protein.
