Today we announce nine new Cancer Grand Challenges, for which Expressions of Interest are now open. These are the obstacles that continue to impede progress against cancer and that no one scientist, institution or country can solve alone. We're inviting international teams to apply for up to $25m of funding to tackle them.
In late 2022, we launched a global conversation to identify our next round of challenges. After a rigorous grassroots process, involving workshops, consultation and debate with the global cancer research community and people affected by cancer, more than 300 ideas were submitted. The Cancer Grand Challenges Scientific Committee met to discuss and debate the ideas, recommending a set of complex challenges, that it believes can be solved.
“These ambitious challenges need bold ideas, extraordinary science and the world’s best minds. I’m excited to see how the global research community plans to take them on," says Professor Sir David Lane, Chair of the Cancer Grand Challenges Scientific Committee.
The deadline to apply is 22 June 2023, and shortlisted teams will be announced in August 2023. Find out more about each of the challenges below:
1. Ageing and cancer | Decipher the functional basis underlying the association between ageing somatic tissues and cancer
Cancer incidence increases dramatically with age and is the leading cause of death in both males and females aged 60-79 years old. Ageing is associated with tissue remodelling and an accumulation of somatic mutations, genome instability, epigenetic alterations, and mitochondrial dysfunction amongst other cellular abnormalities. How distinct ageing processes increase cancer risk at different organ sites remains unclear. No single cellular process associated with an ageing soma sufficiently explains cancer risk across all tissues.
This challenge seeks to understand how ageing-associated molecular changes in somatic cells and immune dysfunction together with endogenous and exogenous environmental factors, impact early cancer initiation in ageing somatic tissues, and organ-specific cancer risk. Find out more
2. Cancer cell plasticity | Understand cancer cell plasticity and its contribution to the development of pan-therapeutic resistance in cancer
Cancer cells show remarkable plasticity in which they can switch lineage and activate latent differentiation programmes, yet the principles governing plasticity in cancer cells remain poorly understood. This plasticity may allow cancer cells to develop stem-like properties, drive invasiveness and metastasis and to evade therapy by developing broad resistance to radiotherapy and cytotoxic chemotherapy.
Increased understanding of cell fate determination through epigenetic reprogramming means that it is timely to study in detail how cancer cells achieve these switching processes. Advanced sequencing technologies are also now available to interrogate single cells and clonal populations. Blocking or exploiting such switching processes could inhibit the recurrence of cancer and eliminate resistant cells after successful primary treatment. Find out more
3. Cancer inequities | Understand the mechanisms through which genetics, biology, and social determinants affect cancer risk and outcomes in diverse populations, to motivate interventions to reduce cancer inequities
Inequities in cancer prevention, screening, and treatment lead to disparities in cancer incidence and mortality and are a major public health concern.
The causes of cancer inequities are complex yet often poorly elucidated. While most inequities are the consequences of social determinants and circumstances (e.g., late-stage diagnosis due to inadequate access to healthcare), there are emerging data that indicate that genetics and biology also play a role. Polygenic scores confer risks that vary by Self-identified Race and Ethnicity (SIRE); genetic ancestry is correlated with cancer risk or outcomes independently of SIRE; and tumour phenotypes and mutational signatures differ by SIRE. Because the relative contributions of genetic, biological, and social drivers of cancer aetiology remain unclear, approaches aimed at reducing inequities remain inadequate. Find out more
4. Chemotherapy-induced neurotoxicities | Understand and prevent chemotherapy-induced neurotoxicity and neuropathy
Many patients suffering from cancer receiving cytotoxic chemotherapeutic agents such as platins and taxanes develop neurological toxicities such as peripheral neuropathy and ototoxicity, which can severely impact their day-to-day functioning and health-related quality of life. The effects on the central nervous system of chemotherapy can also lead to neurocognitive deficits in some patients with long-lasting consequences. This is commonly found after breast cancer treatment, for example. Despite this, there is limited understanding of why this occurs.
Understanding the biological mechanisms of these toxicities would provide insights into the impact of cancer therapies on neurobiology, enable the identification of biomarkers to predict patients at risk, propose strategies to prevent their occurrence, and offer therapeutic solutions to alleviate these debilitating side effects of chemotherapy. Find out more
5. Early-onset cancers | Determine why the incidence of early-onset cancers in adults is rising globally
Since the mid-20th century the incidence of early-onset cancers, defined as cancers diagnosed in adults under 50 years of age, has been rising globally.
In this demographic, cancers in the bone marrow, breast, colorectum, endometrium, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, oesophagus, pancreas, prostate, stomach, and thyroid have increased globally. Some of this may be attributed to the increased implementation of screening programmes, but this does not explain the full picture.
Changes in the exposome and the environment in recent generations may in part explain this observation, including changes in diet, the microbiome, physical activity, obesity, alcohol consumption, sleep patterns, antibiotics use, stress levels, pollution, or environmental contaminants among others.
Understanding and preventing the increase in the incidence of early-onset cancers is now critical to address this emerging global health problem. Find out more
6. Obesity, physical activity and cancer | Determine the mechanisms through which obesity and physical activity influence cancer risk
Obesity and sedentary behaviour are important risk factors for cancer. With over 4 billion adults and nearly 3 million children being overweight or obese, this is a significant global health concern. Previous studies and large meta-analyses have provided convincing evidence that obesity is associated with an increased risk of 13 cancers, and physical activity is associated with reduced risk for 6 different cancer sites. Yet, despite decades of research, the causative mechanisms linking obesity to cancer development and progression are not understood.
The challenge is timely due to recent advances in measurement, data science and emerging artificial intelligence (AI) methodologies, the availability of effective new drugs to treat obesity, experimental policy interventions around the world and new tools from basic science. Together, these provide the foundation for a new era of discovery research to understand the mechanistic links between obesity and cancer that could be translated into effective interventions. Find out more
7. Retrotransposable elements | Understand the roles of retrotransposable elements in cancer
It is now 80 years since Barbara McClintock discovered mobile genetic elements in Maize. Since that discovery the existence and mobilisation of such elements in humans has been broadly established. These elements are both widely dispersed and deeply embedded in our genome. Repressive mechanisms operate to supress their activation, and conversely, they are co-opted by the host to act as gene regulators. Therefore, retrotransposable elements contribute broadly to normal cell function.
Increasing evidence suggests that retrotransposable elements play a role in the initiation and progression of certain types of cancer, but the specific mechanisms are not well understood. Tools now exist to explore the extent of retroelement activation, how cancer cells respond to it, the consequences of genetic instability that retroelement propagation and dispersal causes in cancers as well as how this might contribute to cancer evolution.
Advancing the study of retrotransposable elements would allow a greater understanding of therapeutic vulnerabilities in cancer. Find out more
8. Solid tumours in children | Develop therapeutics to target oncogenic drivers of solid tumours in children
Cancer remains the leading cause of death by disease in children globally, and progress in the treatment of children with solid tumours (which includes brain tumours) has largely stalled. For those children who relapse, there are fewer treatment options available, meaning the outlook is often poor, and outcomes for some paediatric cancers have not improved in more than 30 years.
Despite advances in understanding the biology of most paediatric solid tumours, standard curative treatment regimens continue to rely on cytotoxic agents, developed decades ago, and often radiotherapy. Such therapies induce an alarming rate of severe late effects, including second malignancies, cardiac, neurologic, and skeletal toxicity, and infertility. Targeted therapeutics are needed to improve outcomes for paediatric cancers. Find out more
9. T-cell receptors | Decipher the T-cell receptor cancer-recognition code
Many cancers harbour tumour-infiltrating T cells that are potentially reactive to cancer (neo)antigens. While it is possible to sequence the T-cell receptors (TCR) present on these immune cells, it is presently not possible to use this information to comprehensively and at scale infer the antigen that is recognised by the receptor. Deciphering the T-cell receptor code will allow accurate prediction of the nature of the cancer antigens that T cells detect based on their T-cell receptor sequence. A better understanding of the interaction between the major histocompatibility complex (MHC)-bound antigens and the T-cell receptors has the potential to greatly improve future cancer immunotherapies as well as understanding and treatment of autoimmune and infectious diseases. Find out more