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Cancer Grand Challenges - Rewiring cancer cells

Cancer Grand Challenges

This is a new challenge, which we announced in March 2025. It is open for Expressions of Interest, with the successful team(s) being awarded up to £20m ($25m) to tackle it. Submissions are due by 18 June 2025.

Context

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.

Vision and impact

This challenge will develop novel and creative approaches to rewire cancer cells to a less malignant phenotype and provide proof of concept, fundamentally changing the way we think about cancer treatment. These innovative approaches could lead to an expanded arsenal of therapeutic strategies for cancer that overcome limitations associated with current treatment modalities.

Specialties

Cancer

Oncology

Eligibility Requirements

Addressing this challenge will require methods to determine which cancers or cell types would be susceptible to a particular rewiring approach, and whether further cancer types can be made susceptible using innovative approaches.

Novel ways to target heterogenous tumour cell populations should also be considered, for instance affecting non-responsive cancer cells in a heterogeneous population, by making responding cells more immunogenic, by means of executing an immunogenic form of cell death or by driving cell populations into a more uniform state.

Note that applications should not focus on targeted protein degradation approaches.

An interdisciplinary team will be required, bringing together diverse areas of expertise, which could range from synthetic biology, artificial intelligence, medicinal chemistry and structure-based drug design to expertise in cancer biology, immunology and signalling.

Sponsor Details

Sponsor Institute/Organizations: Cancer Grand Challenges

Sponsor Type: Corporate

Address: 2 Redman Place London, E20 1JQ

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