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The Cancer Grand Challenges program—a joint initiative between Cancer Research UK (CRUK) and the National Cancer Institute (NCI)—has awarded $100 million to four international research teams to address some of the toughest challenges in cancer.

The four winning teams were announced at the Cancer Grand Challenges Summit in Washington, D.C. last week and will each receive $25 million over five years to fund their research.

David Scott, Director of Cancer Grand Challenges at Cancer Research UK, told Inside Precision Medicine that the research the teams will be carrying out is “‘frontier’ science at its most advanced. If we break through these barriers, Cancer Grand Challenges could bring untold advances against cancer’s toughest challenges on a global scale.”

The initiative began in 2015 with Cancer Research UK’s Grand Challenge, which helped global, interdisciplinary teams to work on complex problems in cancer research that had been identified during international workshops with researchers, people affected by cancer, and cancer organizations.

“We’ve made incredible progress against cancer – but there are tough challenges which continue to hold us back, from long-standing gaps in our understanding of complex biological phenomena, to global public health issues where evidence is limited and fragmented. These are the challenges which hold the key to radically different outcomes for people with cancer,” Scott remarked.

In 2020, CRUK partnered with the NCI to launch Cancer Grand Challenges.

“This partnership will support up to 12 new global teams over the next 6 years, bringing the initiative to a whole new level in terms of scale, resource, and ambition,” said Scott.

In 2021, teams were invited to submit funding applications for research focused on nine challenges identified by the Cancer Grand Challenges Scientific Committee which, if solved, could make the biggest difference to progress in cancer research. There were nearly 170 applications, which were then cut down to a shortlist of 11, with four eventual winners.

The winning teams include:

  • CANCAN which will explore the debilitating muscle wasting syndrome cachexia, which is often experienced by patients with advanced cancer. It has a negative impact on quality of life and can limit a patients’ ability to receive systemic cancer therapies. The team will include researchers from 14 institutions across the US and UK, with specialties including oncology, metabolism, neuroendocrinology, immunology, preclinical modeling, clinical research, and advocacy.
  • eDyNAmiC which will use its expertise in cancer biology, genetics, chemistry, evolutionary biology, computer science, mathematics, and clinical research to investigate the creation and action of extrachromosomal DNA which helps tumors evolve and evade treatment. The researchers, from the US, UK and Germany, also aim to develop new ways to target these mechanisms in cancer.
  • NexTGen which will work on the development of next-generation cell therapies for children with solid tumors. The American, British, and French collaborators, from the fields of oncology, immunology, glycobiology, proteomics, mathematics, will also explore whether changing the tumor microenvironment can help make treatments more effective.
  • PROMINENT which hopes to discover what triggers a normal cell harboring oncogenic mutations to transition to a tumor. They include experts in epidemiology, genomics, animal modeling, machine learning, community engagement, and cancer prevention from the US, France, and Spain.

Other challenges in the current round that were not selected for funding this time focused on targeting dormant cancer cells, the risks of E-cigarettes, determining how inflammation causes cancer, delivery of macromolecules to therapeutic targets, and exploiting senescence to improve cancer treatment.

Scott said it is hard to define what makes a winning team stand out “but it’s a combination of a team that works well together, with a good mix of disciplines, backgrounds and experiences, learning to speak each other’s scientific languages and bringing new thinking to a problem that has for too long stood in the way of progress. And passion—the team must bring that passion and motivation to tackling these challenges.”

The Cancer Grand Challenges community now includes more than 700 investigators across 11 teams and 10 countries.

Teams who received previous funding awards have made a number of exciting discoveries such as the development of a novel 3D tumor mapping technology that allowed them to learn how the microbiome drives colorectal cancer, leading to a promising screening test for people with early-stage disease.

Another group have revealed that many carcinogens drive tumorigenesis without directly damaging DNA—challenging the long-held model of tumor development. This in turn has led the current PROMINENT team to explore the Promoter Concept, an alternative model of cancer development and look for new routes to prevention.

Scott explained that although much of the work funded by Cancer Grand Challenges is early-stage discovery research, “in the long term, if successful, all four teams will help us to better understand cancer, which could eventually if not directly impact outcomes for people with the disease.”

“For example, the Solid Tumours in Children challenge team could give new hope to families with children who have solid tumours, where survival has remained stubbornly low for decades, by engineering T cell therapies that will be more effective and with fewer off-target effects than current treatments.”

He added that new standards for managing cancer cachexia could be set and new treatments for resistant cancers could arise from the understanding of extrachromosomal DNA challenge.

“And we may even be able to find new ways prevent cancer from ever happening, which is mind blowing, because we’ve set the challenge of understanding the very early stages of tumour development with the aim of creating a roadmap of the early stages of tumour development, to find new routes to prevention,” Scott concluded.

The next funding Cancer grand Challenges funding rounds are planned for 2023 and 2025.

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