Acquired resistance to apoptosis is a hallmark of most, if not all types of cancer.7
- In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event.8
- Dysregulation of the apoptotic pathways can not only promote tumorigenesis, but can also render cancer cells resistant to conventional anti-cancer agents, since chemotherapy- and radiotherapy-induced killing of cancer cells is mainly mediated through activation of apoptosis.2
Overexpression of anti-apoptotic BCL-2 family proteins (BCL-2, BCL-XL, BFL-1/A1, BCL-W and MCL-1) disrupts the dynamic balance of anti- and pro-apoptotic proteins, which may promote cancer cell survival.2,5
- The overexpression of these proteins is seen in a wide variety of hematologic malignancies and solid tumors.2,9
- The heterogeneity among tumors, even of the same type, necessitates a continued effort to further investigate mechanisms of apoptosis dysregulation in distinct cancer cell types.2
Strategies to inhibit anti-apoptotic BCL-2 proteins include reducing protein expression by targeting the corresponding mRNA with an antisense oligonucleotide as well as blocking anti-apoptotic activity by targeting at the protein level.2,5
- There is interest in developing drugs that mimic the action of the BH3 motif by binding to one or more of the BCL-2-like anti-apoptotic proteins and triggering apoptosis.5