Apoptosis in cancer: from pathogenesis to discovery of advanced selective Bcl-2 family inhibitors

• Main Authors: Samaa Abbas (Author), Nermin S. Abdou (Author), Deena S. Lasheen (Author), Dalal A. Abou El Ella (Author)
• Format: Book
• Published: Ain Shams University, 2019-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: https://dx.doi.org/10.21608/aps.2019.20225; 2356-8380; 2356-8399
• Keywords: apoptosis; Bcl-2; Extrinsic pathway; Intrinsic pathway; Caspase; BH3; Therapeutics. Pharmacology; RM1-950
• Source: Archives of Pharmaceutical Sciences Ain Shams University, Vol 3, Iss 1, Pp 37-54 (2019)

Cancer is a genetic disease characterized by two features: unregulated cell growth and tissue invasion (metastasis). It can be viewed as the result of a succession of genetic changes during which a normal cell is transformed into a malignant one. Evasion of cell death, apoptosis, is one of the essential changes in a cell that cause this malignant transformation. Hence, reduced apoptosis or its resistance plays a vital role in carcinogenesis. The Bcl-2 family of proteins regulates the mitochondrial apoptotic pathway. Disease states arise upon deregulation of the Bcl-2 family of proteins, where cell death is either promoted or evaded; one of the most common tactic cancer cells utilize to promote survival is anti-apoptotic protein overexpression. Specifically, Bcl-2 overexpression has been shown to be a major chemoresistance factor in a number of human cancers, and for this reason, Bcl-2 targeting is a pharmacologic priority in the quest to reactivate cell death for therapeutic benefit in cancer.