Cancer comes back because of heterogeneity.
Synthetic lethality has emerged as a theme that exploits cancer’s innate features to specifically kill cancer but not normal cells. With Olaparib there is one successful example on the market but follow-on approaches have stayed behind expectations. Despite this the field of synthetic lethality has commanded premium deals sizes recently (IDEYA, $100m upfront at pre-clinical from GSK, and 50% royalty on potentially billions of $, $382m market cap currently). Our analysis has revealed that the lack of efficacy of these approaches is caused by heterogeneity of cancer. Tackling phenotypes rather than genotypes should overcome the issues of heterogeneity.
We have created a large scale bioinformatics platform leveraging existing data (no expensive screens) that identifies the networks underlying these phenotypes, identifying both positive controls (such as KRAS and Myc ) but also previously therapeutically unexplored mechanisms including a large number of druggable targets.