Team led by UC San Diego researchers selected for prestigious global cancer prize

(Press-News.org) A global, interdisciplinary team of researchers led by Ludmil Alexandrov, PhD, professor of cellular and molecular medicine and bioengineering at the University of California San Diego, has been selected to receive a Cancer Grand Challenges award of up to $25 million over approximately five years to reveal the underlying mechanisms of mutational signatures, unique patterns of DNA damage caused by environmental exposures or natural cellular processes. By understanding the underlying causes of these signatures, Team CAUSE, which brings together experts from the U.S., the Netherlands and the UK, aims to reshape our understanding of how cancer begins and how it can be prevented and treated. The team is funded by Cancer Research UK, the National Cancer Institute and KWF Dutch Cancer Society through Cancer Grand Challenges. 

“As a global leader in innovation, UC San Diego is committed to harnessing the power of research to develop real-world solutions to improve human health,” said UC San Diego Chancellor Pradeep K. Khosla. “The recognition of Team CAUSE's work is a celebration of our faculty's commitment to driving positive change by addressing some of the most pressing challenges in medicine.”

“This is a tremendous honor both for Dr. Alexandrov and for the entire UC San Diego cancer research community,” John Carethers, MD, vice chancellor for Health Sciences at UC San Diego. "This Cancer Grand Challenges funding is a testament to UC San Diego’s commitment to innovation and collaboration in cancer research, and I look forward to seeing what breakthroughs come to fruition as a result of this science.”

Cancer Grand Challenges is a global research initiative that identifies the toughest challenges in cancer research and empowers a global community of world-class, interdisciplinary research teams to take them on. With awards of up to $25 million, the initiative aims to deliver progress against cancer, giving researchers the resources and flexibility needed to thoroughly explore high-risk, high-reward ideas. The current competition received a record 227 submissions, of which 12 finalists were selected in late 2025. Of those 12, five have been selected for funding.

"Cancer Grand Challenges research and breakthroughs are made possible through our co-founders and visionary partners," said David Scott, PhD, director of Cancer Grand Challenges. "Thanks to their incredible $125 million funding this year, we’re able to unite exceptional research teams from across the globe to tackle the most complex problems in cancer today. Together, we’re creating opportunities for bold team science that could redefine what’s possible for people affected by cancer."

Team CAUSE is working to decipher mutational signatures, which are akin to fingerprints on our DNA, offering clues about the environmental exposures and cellular processes that shape our genetic code. The team will systematically identify and characterize DNA adducts — the chemical modifications to DNA that act as the “pen” writing these signatures. By bridging the gap between the signature and its source, the team is poised to facilitate new breakthroughs into the underlying causes of cancer, ultimately informing more effective prevention and treatment strategies.

"We are thrilled to be part of this prestigious initiative and to have the opportunity to work with a talented team of researchers from across the globe," said Alexandrov, who is also a member of UC San Diego’s Moores Cancer Center. "The framework of Cancer Grand Challenges gives us a unique opportunity to think creatively about major problems in cancer science, integrating research across different disciplines in ways that wouldn’t be possible working in isolation.”

This is not the first experience Alexandrov has had as part of a Cancer Grand Challenges team. Previously, he was a co-investigator on Team Mutographs, which was led by Sanger Institute professor Sir Mike Stratton, PhD, and funded by Cancer Grand Challenges in 2017. Team Mutographs helped pioneer the field of mutational epidemiology and made groundbreaking discoveries in understanding the role of mutations in the development of cancer.

For example, a study published in April 2025, led by Alexandrov and completed as part of the Mutographs research, found that exposure to a specific bacterial strain in early childhood imprints a distinct genetic signature on the DNA of colon cells that increases the risk of developing colorectal cancer before age 50. The new CAUSE team will continue this interrogation of mutations in cancer, now under Alexandrov’s leadership.

"The ability to decode the origins of mutational signatures has the potential to revolutionize our understanding of cancer," added Alexandrov. "We believe that our research will pave the way for new discoveries and new treatments, ultimately improving outcomes for patients worldwide."

END