Cancer Grand Challenges – Rewiring cancer cells
Inhibition of oncogenic signalling in advanced cancers often results in secondary mutations that restore oncogenic signalling in the presence of drugs, indicating that we must consider fundamentally different approaches to treat cancer.
Insights gained over the past two decades have yielded a detailed knowledge of how cells are wired and how proliferation and survival signals are altered in cancer cells. Moreover, advances in synthetic biology, such as proximity-inducing molecules allows proteins that normally would not interact to come together, providing opportunities to change the wiring inside a cancer cell from a signal that promotes oncogenesis to one that has an opposite effect on cancer cells. Emerging approaches to overstimulate oncogenic signalling beyond a cell’s ‘goldilocks’ level, also provide opportunities to steer cells to less malignant phenotypes, as cancer cells may escape the drug-induced overactivation of oncogenic signalling through suppression of intrinsic oncogenic signalling.
This challenge aims to develop inventive ways to rewire cancer cells to a less malignant phenotype as a novel approach to therapy.