venetoclax + azacitidine

Venetoclax + azacitidine is a combination therapy used primarily for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are 75 years or older or who have comorbidities that preclude intensive chemotherapy. Venetoclax is an oral small molecule inhibitor that selectively targets BCL-2 (B-cell lymphoma 2), a protein that prevents apoptosis in cancer cells. By inhibiting BCL-2, venetoclax restores the apoptotic process and promotes cancer cell death. Azacitidine is a nucleoside analog and DNA methyltransferase inhibitor classified as an antimetabolite chemotherapy agent; it incorporates into DNA and RNA to inhibit abnormal cell proliferation and induce differentiation or apoptosis of malignant cells. The combination has demonstrated synergistic effects in AML by not only promoting apoptosis through BCL-2 inhibition but also disrupting energy metabolism in leukemic stem cells via impairment of mitochondrial oxidative phosphorylation (OXPHOS), particularly through disruption of electron transport chain complex II activity in a glutathione-dependent manner[6]. This dual mechanism results in selective targeting and killing of leukemic stem cells. Venetoclax was developed by AbbVie/Genentech (Roche) and marketed under the brand name Venclexta. Azacitidine was developed by Pharmion/Celgene/Bristol Myers Squibb and marketed as Vidaza.

Brand names

VidazaVenclexta

Other names

azacitidine + venetoclax