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| | | | The most urgent, complex problems in cancer research require innovative and collaborative approaches, cutting-edge technologies and bold scientific strategies to drive breakthroughs in prevention, detection and treatment.
Last week, Cancer Grand Challenges – the global research initiative we co-founded with the National Cancer Institute in the US – announced seven new, highly anticipated challenges to address these pressing issues.
With awards of up to £20m, interdisciplinary research teams will be empowered to take on these challenges. Expressions of interest are now open until 18 June 2025.
Cancer Grand Challenges will also be at the AACR Annual Meeting 25–30 April 2025, at booth 2327 to talk about the funding opportunity. |
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| | | | | Developing interdisciplinary AI agents that can generate novel research hypotheses and plans validated through experimentation
The exponential growth of cancer data presents both an opportunity and a challenge. How can we efficiently integrate vast, multi-scale datasets to drive new discoveries?
This challenge will develop interdisciplinary AI agents that go beyond standard data analysis. It requires close collaboration between AI and cancer researchers to generate novel research hypotheses and design experimental approaches. These AI systems will integrate diverse data sources, spanning molecular biology to epidemiology, with a focus on uncovering mechanisms of cancer initiation and progression.
By leveraging human-AI synergy, this work could accelerate paradigm-shifting discoveries and revolutionise the way cancer research is conducted. | | |
| | | | | | | Elucidating the mechanisms underpinning resistance to cancer in high-risk or extremely aged populations
While cancer research has long focused on identifying drivers of malignancy, a fundamental paradox remains: why do some high-risk individuals, such as BRCA1 mutation carriers or heavy smokers, never develop cancer? Similarly, certain progeria syndromes and long-lived species exhibit an unexpected resistance to tumorigenesis.
What are the biological mechanisms that underpin these apparent protective factors, from immune surveillance to metabolic resilience? Understanding these processes could inform novel strategies for cancer prevention and early intervention, ultimately transforming how we approach cancer risk mitigation at both an individual and population level. | | |
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| | | | | Understanding and exploiting opportunities for cancer therapy
Beyond the conventionally studied proteome lies an enigmatic layer of unannotated proteins that aren’t encoded by any known open reading frames or carry sequence alterations without corresponding DNA mutations. These unconventional protein products may hold the key to novel oncogenic mechanisms and untapped therapeutic vulnerabilities.
This challenge aims to elucidate the origins and function of the dark proteome, determining whether it serves as a reservoir of non-mutated tumour-selective antigens or synthetic lethalities that could be harnessed for therapy.
By integrating cutting-edge mass spectrometry, RNA biology and structural analysis, this research could pave the way for innovative immunological and small-molecule-based cancer treatments, potentially offering new "off-the-shelf" therapeutic options. | | |
| | | | | | | Identifying the insults responsible for unexplained mutational signatures
The surge in whole-genome sequencing has revealed an expanding catalogue of mutational signatures, yet the origins of many remain unknown. These mutations stem from DNA repair gone awry, yet their exact nature and sources—whether endogenous or environmental, are poorly understood.
Identifying the precise molecular insults that drive unexplained mutational signatures could bridge that knowledge gap.
Technological innovation will be required to determine the composition of DNA in an unbiased manner, so that it is possible to detect a vast array of potential altered DNA bases and decipher how DNA adducts contribute to the formation of mutations.
This work could transform our understanding of cancer initiation, uncover new cancer causes and lead to new public health measures for cancer prevention. | | |
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| | | | | Understanding the dynamic interactions between the nervous system and cancer
The intricate interplay between the nervous system and cancer remains a largely unexplored frontier in oncology. Emerging evidence suggests that peripheral nerves not only arborise in response to tumour-derived signals but actively contribute to cancer progression, immune evasion, and therapy resistance.
Defining the bidirectional communication between tumours and the nervous system at a mechanistic level could uncover novel therapeutic targets and reveal ways to disrupt neural contributions to tumorigenesis while mitigating cancer-induced neurological and psychological dysfunction.
Bringing together expertise in neuroscience, cancer biology, and immunology, this research could fundamentally reshape our understanding of tumour pathophysiology and lead to innovative treatment strategies. | | |
| | | | | | | Developing novel approaches to disrupt cancer cell signalling
Targeted therapies often lead to adaptive resistance, emphasising the need for radically different approaches to cancer treatment.
Unconventional therapeutic approaches are emerging, such as therapeutic overactivation of oncogenic signalling, illustrating that to achieve durable success in the clinic, we may need to think outside the box.
This challenge seeks to change the wiring inside a cancer cell from a signal that promotes proliferation to one that leads to its downfall. By shifting the paradigm from inhibition to redirection, this research could lead to an expanded therapeutic arsenal that overcomes the limitations of existing precision oncology strategies. | | |
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| | | | Designing methods to identify the functional role of the tumour microenvironment over time
The tumour microenvironment (TME) is not merely a passive landscape but an evolving ecosystem that potentially dictates cancer progression, immune response and therapeutic resistance. While spatial transcriptomics and proteomics have provided static snapshots of TME composition, this challenge aims to take a functional, longitudinal approach, tracking dynamic changes in the TME over time and in response to therapy.
By developing novel tools for real-time, high-resolution analysis of cellular interactions, researchers could uncover new mechanisms of cancer progression and therapeutic resistance, ultimately guiding next-generation treatment strategies that enhance patient outcomes. |
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| | New in Cancer Discovery: tackling cancer through global team science |
| Members of the Cancer Grand Challenges team have authored a perspective article in Cancer Discovery, looking at the new set of challenges in depth.
They also discuss how findings from earlier funded teams have opened up new questions and inspired the new challenges. |
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beating cancer |
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