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International team including Wyss scientists shortlisted for Cancer Research UK’s Grand Challenge

A collaborative project between scientists from the US, UK, Canada and Israel in the run for prestigious award recognizing innovative approaches to fight cancer

By Eriona Hysolli

A multi-disciplinary team of scientists from the University of California San Francisco, Wyss Institute at Harvard University, Stanford University, Institute for Systems Biology at Washington, University of Cambridge, Queen Mary University of London, McGill University and the Weizmann Institute of Science has been shortlisted to the final stages of Cancer Research UK’s Grand Challenge – an ambitious series of £20m global grants tackling some of the toughest questions in cancer research.

In 2017, researchers from the Wyss Institute developed human lung cancer models using its Human Organs-on-a-Chip technology. This image shows lung adenocarcinoma cells growing as a tumor cell colony (yellow) next to normal human small airway cells (red) in the lung epithelial channel of the Lung Cancer Chip. This work was published in Cell Reports. Credit: Wyss Institute at Harvard University

Cancer is commonly thought to be caused by an accumulation of mutations in the DNA of cells that become malignant and invasive, manifested as tumor growth and metastasis. However, a long-standing puzzle in the cancer research field has been the close association between cancer incidence and chronic inflammation (CI). Work from some of the team members, including Donald Ingber, M.D., Ph.D., Founding Director of the Wyss Institute, suggests that inflammation-related changes in tissue structure and mechanics could contribute to the cancer transformation, and that it may be possible to reverse this process by restoring normal tissue properties.

Today’s therapeutics only focus on killing tumor cells but not preventing or reverting their cancerous transformation. The STORMing (STrOmal ReprograMing of Epithelial Cells) team will take a new direction to tackle the cancer challenge by aiming to understand how inflammation influences cancer progression and by developing new therapies that restore  normal tissue structure. Initially the researchers will take a comprehensive experimental approach to analyze cells from the tissues of healthy people and patients with CI-related cancers to identify factors associated with triggering malignancy. Other studies will employ human “organ-on-a-chip” models pioneered at the Wyss Institute to model CI-related cancers as well as animal models of the disease to validate the findings from the patient samples and to develop new cancer-normalizing therapeutics. One novel strategy to be developed, referred to as the “Trojan Horse”, will engineer the body’s own immune cells to deliver payloads that change inflamed tissue to healthy, and thereby eliminate the tumor-inducing environment or reprogram pre-malignant cells to revert to normal.

The team will receive seed-funding of up to £30,000 to draft their full research proposal, and the winning proposal will be announced in autumn 2018.

This is the second round of Cancer Research UK’s Grand Challenge award and last year four teams were awarded up to £20 million each.

Iain Foulkes Ph.D., Executive Director of research and innovation at Cancer Research UK, said: “Round two of Grand Challenge is proving to be incredibly inspiring and the ambitious applications reflect the quality of global researchers this initiative has attracted to beat cancer sooner. We’re delighted with the teams we’ve shortlisted and look forward to hearing more about how they plan to tackle the toughest challenges in cancer research.”

Rick Klausner M.D., Chair of Cancer Research UK’s Grand Challenge advisory panel, said: “The challenges set for Grand Challenge have once again attracted some of the best researchers in the world. I’m looking forward to see how global collaboration could bring together diverse expertise, invigorate areas of research, and overcome barriers in ways that aren’t happening at this point in time.”

“The Grand Challenge gives us an extraordinary opportunity to explore the overlooked role of inflammation in cancer progression and to develop new types of therapeutics that could benefit a large percentage of cancer patients. Our diverse and global team of leading researchers, clinicians, and patient advocates are excited by the possibility of combining  our unique approaches to this problem to develop truly unconventional approaches to cancer prevention and treatment”, said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

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