| Dear Voornaam
In March 2023, we announced a new set of nine Cancer Grand Challenges to bring together a community of world-class researchers with the potential to make transformative progress against cancer.
Today, I’m delighted to share the 12 global teams who have been shortlisted for a Cancer Grand Challenges award, including 27 UK researchers.
The teams unite investigators from 84 institutions across 18 countries in a broad range of disciplines such as statistics, mathematics, population science and computational biology.
We received innovative ideas from the global research community, including proposals to build an unprecedented resource for cancer equity research, decipher how transposable elements and their controllers shape tumour evolution, and to develop oncoprotein degraders to target the drivers of solid tumours in children.
Out of the 178 expressions of interest, the Cancer Grand Challenges Scientific Committee narrowed the innovative ideas down to a shortlist of teams, who will now compete for funding.
The shortlisted teams have until 24 October to send their full application and interviews with the applicants will take place in December.
The winning teams will be announced in March 2024, and each will receive up to £20m in funding to rise above the traditional boundaries of geography and discipline to change outcomes for people with cancer.
Cancer Grand Challenges, an initiative we co-founded with the National Cancer Institute in the US, has invested £210m to date to tackle 10 challenges, uniting a community of more than 700 investigators and collaborators across 10 countries. It is also supported by several partners.
Explore the newest shortlisted Cancer Grand Challenges teams in more detail below.
Kind regards,
Dr Iain Foulkes
Executive Director Research & Innovation
CEO Cancer Research Horizons
Cancer Research UK |
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CHALLENGE: OBESITY, PHYSICAL ACTIVITY AND CANCER Team: COMBAT, led by Lydia Lynch (Harvard Medical School), with investigators across the UK, US, Canada and Ireland.
Team COMBAT hypothesises that metabolism is at the centre of the mechanisms driving obesity-related increased cancer risk and mechanisms that reduce that risk. They aim to identify how obesity fuels cancer, and what are its metabolic weaknesses that can be targeted.
Its proposed approach will involve investigating how whole-body metabolic changes in obesity impact the local metabolism of tumour, immune and stromal cells in the tumour microenvironment; testing carefully designed diets in tumour models to understand the impacts of diet on cancer; and investigating the mechanisms for how obesity interventions act to reduce tumour growth. |
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CHALLENGE: EARLY-ONSET CANCERS Team: PROSPECT, co-led by Andrew Chan (Massachusetts General Hospital) and Yin Cao (Washington University in St. Louis), with investigators across the UK, US, France, India and Italy.
Team PROSPECT hopes to tackle the rise in the incidence of early-onset colorectal cancer (EOCRC) by employing a disruptive, transdisciplinary approach spanning cells, individuals and populations.
The team aims to define the lifetime exposures (exposome) and transmission dynamics associated with EOCRC, to identify novel risk factors as well as prevention strategies for this cancer type. This would involve multi-omic profiling approaches to data and samples from studies derived from racially and geographically diverse at-risk cohorts. |
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CHALLENGE: CANCER INEQUITIES Team: SAMBAI, led by Melissa Davis (Morehouse School of Medicine), with investigators across the UK, US, Ghana, and South Africa.
SAMBAI aims to build an unprecedented resource focused on breast, prostate and pancreatic cancer in people of African descent.
They hope to generate a comprehensive, accurate and relevant measurement of social, environmental, genetic and immunological factors that can be used to define the factors that cause and influence disparate outcomes in diverse underserved populations.
The team envisions that its approach will allow for the clarification of critical cancer inequalities research questions and provide unparalleled international datasets for testing hypotheses to produce global action to overcome cancer inequities. |
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CHALLENGE: CANCER CELL PLASTICITY Team: PLASTICITY-Tx, led by Cédric Blanpain (Université libre de Bruxelles), with investigators across the UK, Belgium, US, Spain, Israel, France and Austria.
PLASTICITY-Tx hopes to uncover the mechanisms that drive cancer cell plasticity and leverage this information to devise pharmacological interventions that can interfere with these processes.
The team hopes to integrate transcriptional, epigenetic and spatial single-cell analysis techniques to construct comprehensive catalogues encompassing the various cancer cell states and those in associated stromal cells. The team would utilise a variety of models to track cell state transitions and uncover the cell-intrinsic genetic determinants and microenvironmental regulators that influence cancer cell plasticity. |
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CHALLENGE: RETROTRANSPOSABLE ELEMENTS Team: decrypTEd, led by Didier Trono (École Polytechnique Fédérale de Lausanne), with investigators across the UK, Switzerland, France and US.
The decrypTEd team hopes to define the roles of transposable elements (TEs) and their epigenetic controllers in tumour evolution and use the resulting knowledge to develop novel cancer therapeutics.
TEs and their KRAB zinc finger protein (KZFP) controllers, which bind to and silence repetitive sequences, are major drivers of genome evolution in vertebrates. The team would investigate how TEs and KZFPs are deregulated throughout cancer, focusing on lung, breast and colon cancers and leukaemia, and create the first multi-dimensional single-cell atlas of TEs. |
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CHALLENGE: CHEMOTHERAPY-INDUCED NEUROTOXICITIES Team: RESCuE, co-led by Michelle Monje (Stanford Medicine) and Alison Lloyd (University College London), with investigators across the UK, US, Canada, Germany and Netherlands
Using powerful tools of modern neuroscience, coupled with expertise in the cancer field, the RESCuE team aims to take an ambitious, interdisciplinary approach to address the cause, consequence and cure of chemotherapy-induced neurotoxicities in the central nervous system and peripheral nervous system.
Focused on chemotherapy-related cognitive impairment (CRCI) and chemotherapy-induced peripheral neuropathy (CIPN) in adults and children, the team hopes to provide an unparalleled analysis of chemotherapy-induced neurotoxicities, define the biology underlying risk and generate new screening platforms for treatment development. |
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CHALLENGE: SOLID TUMOURS IN CHILDREN Team: PROTECT, led by Stefan Pfister (Hopp Children's Cancer Center Heidelberg (KiTZ)) with investigators across the UK, Germany, US and Spain.
PROTECT’s focus is on major cancer-driving proteins in Ewings sarcoma, neuroblastoma, synovial sarcoma, ependymoma and high-grade glioma, using different approaches to target these as yet undrugged cancer drivers and overcome resistance to available targeted inhibitors.
The team aims to test drug candidates that are at different stages of the drug development pipeline, including degraders and small molecule kinase inhibitors. Its overarching objective is to establish a platform for repeated developmental cycles of paediatric-specific drug development for emerging targets. |
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CHALLENGE: T-CELL RECEPTORS Team: MATCHMAKERS, led by Michael Birnbaum (Massachusetts Institute of Technology), with investigators across US, Netherlands, Norway and Germany.
MATCHMAKERS’ overarching goal is to predict what T cells recognise in individual tumours using simple laboratory tests and computational prediction. To make this goal a reality, the team hopes to develop novel methods and new algorithms, and create large, integrated datasets of T-cell receptors (TCRs) and peptide-major histocompatibility complexes (MHCs).
Uniting world leaders in cancer immunology, genetics, high throughput method development, structural biology and computer science, the team hopes to ultimately use its approaches to generate tumour antigen-specific TCRs for use in personalised immunotherapies. |
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CHALLENGE: CANCER CELL PLASTICITY Team: OPTIMAL, led by Ronald Evans (The Salk Insitute for Biological Studies), with investigators across the UK, US and Netherlands.
OPTIMAL’s overarching aim is to determine how cell plasticity contributes to therapeutic resistance. To achieve this, the team hopes to explore the hypothesis that cancer co-opts the normal pathways of plasticity that are needed for cellular repair and regeneration in order to promote cancer cell plasticity and therapeutic resistance.
The team aims to look at how plasticity is regulated by the tumour microenvironment over space and time; define how alterations in whole-body homeostasis influence cancer cell plasticity; and identify pathways involved in maintaining the plastic state that can be targeted to improve therapeutic outcomes. |
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CHALLENGE: EARLY-ONSET CANCERS Team: Pandora, led by Dean Jones (Emory University) with investigators across US, Canada, Israel, Mexico and Netherlands.
Early-onset cancers (EOCs) have been on the rise over the past 60 years. Pandora hopes to identify mechanisms linking the exposome (an individual’s lifetime exposures) during critical windows of development, including before birth and in early life, to multiple types of EOC.
With access to an unparalleled birth cohort of 20,000 pregnancies followed for 60 years over three generations (60,000 individuals), the team hopes to apply novel high-dimensional methods of interrogating the exposome to identify specific exposures and associated gene and metabolic reprogramming linked to EOC. |
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CHALLENGE: SOLID TUMOURS IN CHILDREN Team: KOODAC, led by Yael Mossé (Children’s Hospital of Philadelphia), with investigators across the UK, US, France, Germany and Austria.
There is a major unmet clinical need for children with oncogene-driven cancers. To address this, the team hopes to develop orally bioavailable drugs that can cross the blood-brain barrier that will dramatically improve cure rates for children with high-risk, oncogene-driven cancers.
The team hopes to focus on the development of Targeted Protein Degraders (TPDs) and Molecular Glue Degraders (MGDs) to target five key and previously undruggable oncoproteins (MYCN, EWSR1-FLI, DNAJB1-PRKACA, ALK, and PAX3/7-FOXO1), and conduct the preclinical studies needed for biomarker-driven clinical trials. |
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CHALLENGE: CANCER CELL PLASTICITY Team: CaPTr, led by Andrew Feinberg (Johns Hopkins University) with investigators across the UK, US and Israel.
Cancer plasticity is a result of epigenetic dysregulation, which allows cancer cells to transition away from their normal behaviour in a stochastic way (like a random walk), allowing them to evolve to survive, proliferate, spread and evade the immune system and chemotherapy.
CaPTr hopes to capture and combat this poorly understood transition state that has eluded precise detection because it changes dynamically, and which is currently not targeted by existing cancer therapies. The project would involve the development of the first quantitative framework based on integration of concepts from physics, mathematics, biology and genomics, supported by extensive experimental validation and analysis, to link epigenetic reprogramming to genetics, signalling networks and environmental cues in cancer. |
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Funding & Research Opportunities |
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| | | Applications accepted all-year round |
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| | | Applications accepted all-year round |
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| | | Online 4:00 PM 27 September 2023 |
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| | | Paris, France 04 October 2023 |
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| | | Liverpool, UK 18 October 2023 |
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| | | Cambridge, UK 03 November 2023 |
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| | | London, UK 14 November 2023 |
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| | | Manchester. UK 17 November 2023 |
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| | | London, UK 21 November 2023 |
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| | | Manchester, UK 27 February 2024 |
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