In honor of the Ham-Wasserman Lecture by Andrew Roberts at #ASH20, I'd like to share some of the key #venetoclax content published in @CD_AACR over the past few years:
From 2014, by @DrTonyLetai @mkonople and colleagues, early preclinical evidence that BCL-2 inhibition would be effective in AML https://cancerdiscovery.aacrjournals.org/content/4/3/362.long
Their phase II trial in 2016 show clinical proof of concept, and venetoclax was ultimately approved for use in AML https://cancerdiscovery.aacrjournals.org/content/6/10/1106.long
A study in 2017 by @lane_andy and colleagues suggested venetoclax would also have activity in rarer malignancies such as BPDCN https://cancerdiscovery.aacrjournals.org/content/7/2/156.long
As venetoclax use extended into CLL, Piers Blombery, Andrew Roberts, and colleagues showed that acquisition of BCL2 mutations conferred venetoclax resistance in patients with CLL, suggesting venetoclax's on-target activity (published with an #ASH18 LBA!) https://cancerdiscovery.aacrjournals.org/content/9/3/342.long
Three recent papers in 2019-2020 looked at mechanisms of venetoclax resistance in AML - one by @xufeng_chen @glytsou @iannisaifantis1 and colleagues implicated mitochondrial components https://cancerdiscovery.aacrjournals.org/content/9/7/890.long
Another paper by Jeff Tyner and colleagues focused on the role of the TP53 apoptotic network https://cancerdiscovery.aacrjournals.org/content/9/7/910.long
And another by @SSP_PEI @DanPollyea @CraigTJordanLab and colleagues investigated the role of monocytic subclones https://cancerdiscovery.aacrjournals.org/content/10/4/536
Most recently, work by Tamar Uziel & colleagues @abbvie looked at the effect of venetoclax on T cells and found that BCL-XL promotes survival in effector T cells following BCL-2 inhibition and that venetoclax enhanced the effect of PD-1 inhibition in vivo https://cancerdiscovery.aacrjournals.org/content/early/2020/09/04/2159-8290.CD-19-0759.long