Cancer Grand Challenges

The National Cancer Institute (NCI) and Cancer Research UK (CRUK), the world’s leading funders of cancer research, are partnering to fund the Cancer Grand Challenges (CGC) program. Cancer Grand Challenges will fund novel ideas by multidisciplinary research teams from around the world that offer the potential to advance bold cancer research and improve outcomes for people affected by cancer.

Cancer Grand Challenges is a global funding partnership giving multidisciplinary teams of scientists the flexibility and scale to innovate and carry out cutting-edge research. This partnership fosters a highly competitive process designed to promote scientific creativity of the highest order. Through this partnership, NCI and CRUK expect to fund around four awards for each round of Cancer Grand Challenges, with each multidisciplinary team being awarded approximately $25 million over five years.

The timeline for the 2021 Challenge questions is listed below and will be updated regularly:

Launch of Cancer Grand Challenge Questions	10/14/2020
Submit Expression of Interest	4/22/2021
Announcement of Those Selected to Submit Full Application	06/2021
Interviews	12/2021
Final Teams Publicly Announced	2022

To learn more, visit the cancer grand challenges program website.

For any inquiries, please email NCICancerGrandChallenges@mail.nih.gov.

Open Cancer Grand Challenges

The nine challenges were developed through a series of international workshops and an open call online that collected ideas from the cancer research community and people affected by cancer. Of these, the most compelling were reviewed and selected by an expert panel with input from a patient committee.

• Understand how cells and tissues maintain “normal” phenotypes while harboring oncogenic mutations and how they transition to become a tumor
  Why some cells but not others can resist becoming cancerous remains a mystery. Researchers suspect that factors such as aging, the immune system, and a cell’s location could all contribute. This Cancer Grand Challenge asks scientists to answer the deep biological questions around what makes our cells “normal,” helping them discover what exactly transforms ordinary cells into cancer cells.

• Systematically deliver macromolecules to intracellular targets for therapeutic benefit in cancer
  Getting drugs inside the cancer cells they need to destroy is a major problem that scientists face when designing new treatments. This task is particularly challenging for larger and more complex drugs—known as macromolecules—that are too big to slip into cells without help. This Cancer Grand Challenge invites scientists from across disciplines to work together to develop new ways to deliver our most promising macromolecule drugs to every cell in the body, including hard-to-reach places like the brain.

• Understand and exploit senescence to improve cancer treatment
  When cells are put under stress, such as when their DNA is damaged, they can enter a state called senescence, in which they stop dividing. Senescence can help protect us against cancer, as it forces potential cancer cells to stop dividing before it is too late. Research suggests that cancer cells can become senescent too, halting their growth. This raises important questions: can we trigger senescence in cancer cells? And can we find ways to target and eradicate these cells from the body? For this Cancer Grand Challenge, we are looking for a multidisciplinary team to manipulate this process to eliminate cancer cells from the body.

• Determine the potential benefits and risks of e-cigarette use
  The effects of e-cigarette use on tobacco use behavior and tobacco-related health outcomes are still emerging and much remains to be learned. This Cancer Grand Challenge invites experts around the world to come together and examine the harms and potential benefits of e-cigarette use from a global perspective. By bringing these professionals together, we can provide robust answers to crucial questions, including: How do e-cigarettes influence overall tobacco use, including initiation, dual use, and cessation? What are the short and long-term health consequences of e-cigarette use? How does the regulatory context affect the extent of harms and potential benefits of these products?

• Determine how inflammation causes cancer
  Despite being crucial to our health, inflammation can cause serious damage to our body if it spirals out of control, making it a major risk factor for cancer. Astoundingly, an estimated 20–25% of cancers are linked to chronic inflammation globally; however, we do not understand the relationship between inflammation and cancer, including how many types of inflammation exist, and which can cause the disease. This Cancer Grand Challenge asks researchers to untangle the complex web of interactions involved in inflammation and pinpoint which processes cause cancer.

• Develop novel therapies to target unique features in solid tumors in children
  We are beginning to understand that tumors in children are very different from those in adults. If we could understand more about these differing elements and find ways of targeting them, we could create new drugs or reuse existing ones to better treat children’s cancer. This is what this Cancer Grand Challenge focuses on—taking a different approach to find new ways to help children survive solid tumors.

• Understand the biology of extrachromosomal DNA (ecDNA) generation and action and develop approaches to target these mechanisms in cancer
  New research has revealed that cancer cells create vast numbers of extrachromosomal DNA (ecDNA) loops, often containing many copies of genes that help the cancer grow and survive. If we can learn how ecDNA forms and changes in cancer, we could create brand new therapies that target it. This Cancer Grand Challenge invites researchers to harness the latest genetic technologies and draw on new knowledge gained from studying ecDNA in microorganisms to make this possible.

• Identify and target dormant cancer cells
  Even after apparently successful treatment, cancer can unfortunately return, sometimes growing and spreading rapidly many years after the initial diagnosis. This makes it very difficult to detect. But what causes these cells to become dormant, how and where they hide, and what revives them are all unknown. This Cancer Grand Challenge aims to shed light on these unknowns. By unravelling the mystery of cancer cell dormancy, researchers could find ways to detect these dangerous cells and then eliminate them or stop them from waking up.

• Understand and reverse cachexia and declining performance status in cancer patients
  In the late stages of cancer, people often experience extreme weight loss and muscle wasting—a condition called cachexia. These individuals’ general well-being can also deteriorate in other ways—they become weak and tired, with even everyday activities becoming overwhelming. To develop better ways to help people whose health deteriorates in this way, this Cancer Grand Challenge invites multidisciplinary teams to find bold new ways to understand the complicated pathways involved.