Just watched a video on MCL-1 and thought our group might be interested (if not already aware!).
From the CLL Society website:
As good as venetoclax is as a single agent, there are now many studies that show even more remarkable responses occur when it is used in combination with ibrutinib or rituximab. See this on the Murano trial from ASH 2017 that combined V+ rituximab. We soon will share the V+I data from ASCO 2018.
An MCL-1 inhibitor combo with V, if safe and tolerable, might seal the deal in CLL. Only time and trials will tell.
Here is my interview with my friend and CLL Society Medical Advisory board member, Dr. Rick Furman from ASH 2017
Watch this short video in plain language about MCL-1.
provides an excellent example of the trials and tribulations of searching for an effective small molecule inhibitor for MCL-1. The figures at the end of the paper (past the references) show just how the small molecules must bind to a specific groove in the MCL-1 protein in order to block its antiapoptotic activity.
Heather and Chris, the links that you provided relative to MCL-1 are wonderful, and have led me to spend more time reading about MCL-1 and ways to target it. I am particularly interested since I’m 17p deleted, now on ibrutinib, and anticipating treatment at some point with venetoclax. I was interested to learn that in folks who fail venetoclax treatment a common reason can be due to elevated levels of MCL-1. In addition to the small molecules targeting MCL-1 highlighted in your post Chris, I see that cdk4/6 kinase which is required for MCL-1 function is being targeted in an open Phase 1 trial testing the safety of the cdk4/6 inhibitor Voruciclib/P1446A-05. clinicaltrials.gov/ct2/show.... The trial is open for CLL as well as DLBCL.
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