BIM is Big

Discussions to date in relation to pro-survival proteins have centred on drugs targeting Bcl-2 e.g. Venetoclax. Bcl-2 keeps cells alive by binding to and suppressing BIM which triggers cell death. From what I understand, Bcl-2 is actually a family of proteins which also include Mcl-1 and Bcl-x.

One of the presentations at the 29th Lorne Cancer Conference 2017 held in February was, Which pro-survival BCL-2 family member should be targeted for the treatment of which cancer? The presentation was by Andreas Strasser from the Walter+Eliza Hall Institute. It would appear that Mcl-1 is critically important in a range of cancers including c-Myc driven malignant lymphoma.

The importance of Mcl-1 hasn't escaped the notice of Doug Fairlie.

Fairlie contributed to the research paper, MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib, published in December 2016. The data from the study provided the first evidence that Mcl-1 drives breast cancer cell invasion and that Mcl-1 antagonists could be used alone or in combination to suppress metastasis.

The work by Fairlie is being progressed through the project funded by NHMRC, a collaboration between Phylogica, ONJCRI and others. If you refer to the Phylogica announcement of 5 December 2016, you will note that the pro-survival proteins of interest include Mcl-1.

The presentation by Phylogica from January 2017 includes slide 56 titled Synergistic targeting of Myc and pro-survival proteins. The dot point of interest is FPP-Bim targets all pro-survival proteins: Bcl-2, Bcl-x and Mcl-1.

Do we deduce that the FPP-Bim can simultaneously target all pro-survival proteins? This could be big.