BCL-2 inhibition is a logical approach to inducing apoptosis in haematological malignancies1-5
Dysregulation of the BCL-2 family of proteins is a fundamental characteristic of many haematological cancers3,4
- Increased expression of BCL-2 is associated with a wide variety of haematological malignancies, including chronic lymphocytic leukaemia, acute myeloid leukaemia, and follicular lymphoma, as well as solid tumours in the brain, breast, lung, prostate, and pancreas2,3
- In some cancer cells, overexpressed BCL-2 can bind and inactivate the pro-apoptotic proteins6
- Cancer cells with a large pool of bound and inactivated pro-apoptotic proteins have the potential to be displaced from BCL-2 to trigger apoptosis1,2,5
The significant apoptotic potential of these cancer cells suggests that BCL-2 is a rational target for therapeutic intervention.1
BCL-2=B-cell lymphoma 2.
References: 1. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324-1337. 2. Plati J, Bucur O, Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb). 2011;3(4):279-296. 3. Chen A, Madu CO, Lu Y. The functional role of Bcl-2 family of proteins in the immune system and cancer. Oncomedicine. 2019;4:17-26. 4. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-70. 5. Fulda S, Gorman AM, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol. 2010;2010:214074. 6. Tzifi F, Economopoulou C, Gourgiotis D, Ardavanis A, Papageorgiou S, Scorilas A. The role of BCL2 family of apoptosis regulator proteins in acute and chronic leukemias. Adv Hematol. 2012;2012:524308.