Bcl2 is a family of proteins that are involved in the inhibition of apoptosis in cells. My question is that what makes this anti-apoptotic protein useful in cancer therapies as opposed to focusing on pro-apoptotic proteins? Are Bcl2 proteins simply easier to work with as opposed to the pro-apoptotic proteins? Or Bcl2 proteins have some sort of other characteristic that has allowed them for be the target for cancer therapies?

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    $\begingroup$ I don't have time for a full answer now, but the very quick explanation is that by inhibiting Bcl2 activity, you promote apoptosis. Bcl2 proteins are inhibitors, and by inhibiting the inhibitor you activate whatever process you're looking at. $\endgroup$ – MattDMo Nov 24 '15 at 19:39

Bcl2 is an anti-apoptosis protein, meaning that by inhibiting Bcl2 you will inhibit its anti-apoptotic effects. In other words, by inhibiting Bcl2 you actually induce apoptosis in cancer cells. This is one of those concepts in biology that can be hard to follow... that is, "by inhibiting an inhibitor you cause activation".

Cancer cells in particular seem to be resistant to the endogenous pathways in the cell leading to apoptosis, and the reasons for this phenomena are an area of active research. There are two major pathways of apoptosis within the cell, the extrinsic pathway the involves caspase proteins and the intrinsic pathway that involves Bcl2 and a number of other proteins associated with the mitochondria.

Bcl2 is part of a family of proteins that are involved in the intrinsic pathway of apoptosis - for a great and recent review see this recent review... or search on PubMed for a number of recent review articles.

Interestingly, cancer cells have a particular type of mitochondrial dysfunction that may be related to Bcl2, which is still incompletely understood. Cancer cells somehow inhibit the intrinsic apoptotic pathway, which involves the mitochondria. Additionally, cancer cells decrease aerobic metabolism by the mitochondria and preferentially use anaerobic metabolic processes instead - called the "Warburg Effect" by individuals in the metabolism and cancer fields. This was originally described by Otto Warburg almost 100 years ago - i.e. that cancer cells preferentially use anaerobic metabolism - but why this occurs is still unknown to present day.

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