BH3 mimetics activate multiple pro-autophagic pathways

Mitochondrial apoptosis and BH3 mimetics

The BCL2-selective BH3 mimetic venetoclax was recently approved for the treatment of relapsed, chromosome 17p-deleted chronic lymphocytic leukemia (CLL) and is undergoing extensive testing, alone and in combination, in lymphomas, acute leukemias, and solid tumors. Here we summarize recent advances in understanding of the biology of BCL2 family members that shed light on the action of BH3 mimeti...

On BH3 Mimetics and Ca2+ Signaling

Preclinical Research BH3 mimetics are anticancer agents that reproduce the spatial arrangement of the BH3 domain of Bcl-2 family proteins. Just like the BH3-only proteins, these compounds bind to the hydrophobic cleft of the pro-survival Bcl-2 members such as Bcl-2 or Bcl-xL, and disrupt their heterodimerization with pro-apoptotic Bax or Bak, sensitizing cells to chemotherapy. In recent years, ...

BET-inhibitors as sensitizers for BH3-mimetics

BH3 Mimetics for the Treatment of Prostate Cancer

Despite improved diagnostic and therapeutic intervention, advanced prostate cancer (PC) remains incurable. The acquired resistance of PC cells to current treatment protocols has been traced to apoptosis resistance based on the upregulation of anti-apoptotic proteins of the Bcl-2 family. The use of BH3 mimetics, mimicking pro-apoptotic activator or sensitizer proteins of the intrinsic apoptotic ...

BH3 mimetics and multi-kinase inhibition in AML.

In this issue of Blood, Rahmani et al show in preclinical studies that the combination of the multi-kinase inhibitor sorafenib with the BH3 mimetic obatoclax results in enhanced antileukemic effects compared with the effects of each agent alone. This work has important clinical implications because it describes a novel approach to overcome acute myeloid leukemia (AML) cell resistance by combini...