$25 Million to Decode Cancer's Chemical Fingerprints

Every cancer carries a record of what damaged it. Scattered across the tumor genome are clusters of mutations arranged in patterns - patterns distinctive enough that researchers can sometimes identify their cause the way a forensic scientist reads a wound. Cigarette smoke leaves one signature. Ultraviolet radiation leaves another. Some patterns point to failures in the cell's own repair machinery. Researchers call these mutational signatures, and they have spent years cataloguing them.

The harder question is not what the signatures look like but what, exactly, at the chemical level, wrote them. Answering that question is what a newly funded international team will spend the next five years trying to do.

What Cancer Grand Challenges Actually Means

Cancer Grand Challenges is a joint initiative of Cancer Research UK, the US National Cancer Institute, and KWF Dutch Cancer Society. It does not fund incremental research. The model is explicitly built around large, coordinated teams tackling problems that have resisted conventional approaches. This year's competition attracted 227 submissions. Twelve teams reached the finalist stage. Five received funding.

Team CAUSE, led by Ludmil Alexandrov of the University of California San Diego, was one of them. The award is up to $25 million over approximately five years - substantial enough to support the kind of sustained, multidisciplinary effort the question requires. Team members come from the US, the Netherlands, and the UK.

Alexandrov holds a joint appointment in cellular and molecular medicine and bioengineering at UC San Diego and is a member of the Moores Cancer Center. He is not new to this territory. He was a co-investigator on Team Mutographs, an earlier Cancer Grand Challenges project led by Sir Mike Stratton at the Sanger Institute. Mutographs helped establish the field of mutational epidemiology and produced findings about how mutations accumulate across different cancer types. A 2025 study from that work identified a bacterial strain encountered in early childhood that leaves a specific genetic signature on colon cells - a signature associated with early-onset colorectal cancer.

The Chemical Bridge

What Team CAUSE is attempting goes a step deeper. Mutational signatures tell researchers what damage pattern is present in a tumor. But the link between that pattern and its environmental or biological source has often been inferred rather than demonstrated at the molecular level.

The mechanism that physically writes a mutation into DNA is a chemical modification called a DNA adduct - a point where a chemical compound has bonded to the DNA molecule. Adducts distort the DNA structure, causing errors when the cell copies its genome. Different chemicals produce different adducts, and different adducts produce different patterns of mutation. Team CAUSE will work to systematically characterize these adducts - essentially, to identify the specific chemical pen that wrote each signature.

If successful, this creates a more complete chain of evidence: from environmental exposure or cellular malfunction, through chemical modification of DNA, to a specific mutational pattern, to cancer risk. That chain has practical implications for prevention - identifying exposures that cause specific signatures could direct public health interventions toward those sources - and potentially for treatment, if certain signatures indicate vulnerabilities that drugs can exploit.

What Success Would Look Like

It is worth being realistic about the timeline. Deciphering the molecular origins of mutational signatures is technically demanding work. The chemical modifications involved can be present at extremely low levels in biological samples. The experimental systems needed to link specific adducts to specific signatures require careful design to avoid confounds. This is high-risk, high-reward science of the kind Cancer Grand Challenges was designed to support.

David Scott, director of Cancer Grand Challenges, described the competition's ambition in terms of enabling "bold team science that could redefine what's possible for people affected by cancer." Whether Team CAUSE's approach fulfills that potential depends on whether the chemistry cooperates and whether the insights transfer from experimental systems to the messy reality of human tumors in diverse environments.

What the award does guarantee is that the question will get a serious, sustained, well-resourced attempt at an answer. Given what understanding cancer's chemical fingerprints might eventually mean for prevention and treatment, that seems like a reasonable place to direct $25 million.