Collaborative project will study a new way to tackle cancers caused by chronic inflammation
By Lindsay Brownell
The Wyss Institute’s Founding Director Donald Ingber, M.D., Ph.D. has been named by Cancer Research UK as a member of a global research team funded through its Grand Challenge competition – an international funding initiative that brings together the brightest scientists from around the world and from different disciplines to answer some of the biggest questions facing cancer research.
This pioneering team, comprised of eleven investigators and four patient advocates across multiple continents, was shortlisted for the prize in early 2018 and has now been awarded ~$25 million to uncover how chronic inflammation causes cancer, joining the ranks of the growing community of Grand Challenge researchers.
Edward Harlow, Ph.D., member of the Grand Challenge advisory panel and Professor of cancer education and research at Harvard Medical School, said, “I’m not aware of any funding opportunities anywhere in the world that can begin to integrate this many international cancer experts on projects of such clear importance. These teams have been brought together to tackle many of the biggest challenges we currently face in cancer research. We can see from the progress already achieved how powerful it is to support collaborations of this scale.”
Inflammation is part of the body’s immune response, and occurs when white blood cells release chemicals to help protect it from damaged cells, foreign substances, or infections. Chronic inflammation, which lasts much longer than a typical inflammatory response, can be caused by several factors, such as viral and bacterial infections, being overweight, or lack of exercise, and can lead to more diseases including cancer.
We hope to make a major advance in the treatment of chronic inflammation-associated cancers, which represent almost 25% of all human cancers.
Work from multiple laboratories, including pioneering work from Ingber’s lab beginning over twenty-five years ago, has shown that the non-cancerous cells and extracellular matrix surrounding tumor cells, or what is known as the “stroma,” can control whether or not the cancer grows or disappears. Inflammation of the stroma could impact its ability to keep neighboring cancer cells in check. The aim of this Grand Challenge project is to determine whether it’s possible to treat the non-cancerous stromal cells, rather than attacking the cancer cells directly, with the ultimate goal of creating new treatments to prevent cancer from developing in patients with chronic inflammatory diseases.
The team is being led by Thea Tlsty, Ph.D. at the University of California, San Francisco, along with collaborators from the U.S., Canada, the UK and Israel. “Cancer arises from conversations between epithelial and stromal cells,” said Tlsty. “If I take epithelial cells normally incapable of generating tumors and put them next to stromal cells from a cancerous area, the injured stroma sends signals that turn these epithelial cells into cancer. But if I take epithelial cells from the most horrible cancer imaginable and surround it with healthy stroma, the tumor-forming capacity of these epithelial cells will be suppressed, suggesting that the stroma is dominant. Our project will enable us to uncover how the surrounding stromal environment affects cancer development and where inflammation plays a role in this,” said Tlsty.
The researchers plan to take a comprehensive experimental approach to analyze cells from the tissues of healthy people and patients with inflammation-related cancers to identify inflammatory factors that could be triggering cancer malignancy. These studies include employing the human Organ Chip technology pioneered by Ingber’s lab at the Wyss Institute to model inflammation-related cancers, as well as animal models of the disease to validate the findings from patient samples and to develop new therapeutics. Additionally, the team’s novel “Trojan Horse” strategy will engineer the body’s own immune cells to deliver payloads that change inflamed tissue to healthy tissue, thereby eliminating the tumor-inducing environment and potentially causing pre-malignant cells to revert to normal cells.
“I am very excited to be part of an incredibly talented multi-disciplinary and multi-national effort that will confront the challenge of understanding how normal stromal tissues can influence the development of cancer in order to develop potential new cancer reversal therapies, which is an area that has intrigued me personally since the time I was a graduate student. By attacking this problem using forefront imaging, genomics, bioinformatics, and bioengineering technologies in combination with clinical specimens, we hope to make a major advance in the treatment of chronic inflammation associated cancers, which represent almost 25% of all human cancers.” said Don Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, and Professor of Bioengineering at Harvard’s School of Engineering and Applied Sciences.
Iain Foulkes, PhD, Cancer Research UK’s executive director of research and innovation, said:
“Individually, these research teams are among the best in the world in their respective fields. By bringing them together across borders, Grand Challenge is enabling these teams to think bigger and establish new and exciting collaborations. The scale of the funding reflects the opportunity we see in harnessing their ability to understand and tackle cancer.”
The other members of the research team include Uri Alon from the Weizmann Institute of Science, Lorenzo Ferri from McGill University, James Goldenring from Vanderbilt University School of Medicine, Sui Huang from the Institute for Systems Biology in Seattle, Stuart McDonald from the Barts Cancer Institute at Queen Mary University of London, Garry Nolan from Stanford University, Morag Park from the Goodman Cancer Research Centre and McGill University, Kole Roybal from the University of California at San Francisco, Doug Winton from the Cancer Research UK Cambridge Institute, and patient advocates Desiree Basila, David Chuter, Deborah Collyar, and Ann Russell.