Buck Faculty Judith Campisi, PhD, Gets Funding to Tackle a "Provocative Question" in Cancer Research

The National Cancer Institute (NCI) is going after the major unsolved or neglected problems in oncology. And they’re asking Buck faculty Judith Campisi, PhD, to help them do it. Campisi will receive more than $420,000 to grapple with one of 24 “provocative questions” aimed at stimulating NCI’s research community. Her question: How does the lifespan of an organism affect the molecular mechanisms of cancer development, and can we use our deepening knowledge of aging to enhance prevention or treatment of cancer?

“In the developed world, 90 percent of the cancers seen in the clinic are in people 50 years or older,” said Campisi. “Understanding which features of aging change the rate of tumor incidence would allow researchers to identify potential biological processes that could be targets for prevention and therapy.”

Cancers have been commonly associated with aging presumably because of the accumulation of mutations affecting cancer genes. But Campisi says mutations aren’t necessarily enough to give cancer a foothold in the body. Her project will delve into cellular senescence – the process that occurs when cells permanently lose the ability to divide – and its role in the development of cancer.

Senescence has long been seen as a defense against cancer – damaged cells shut down when they become at risk of proliferating uncontrollably. But groundbreaking research in the Campisi lab has shown that senescence comes with a price. Cells spew inflammatory cytokines when they enter the “zombie” state associated with senescence. Campisi says the inflammation can harm nearby cells in ways that promote cancer. “We think senescence helps create an environment in the tissues that encourages cancer to grow,” said Campisi. “Given the fact that we have more cells becoming senescent as we age, we think this could explain the patterns of carcinogenesis we see during the aging process.”

Campisi’s “provocative question” research will take place in mice and involve a collaboration with the Melov lab. The scientists will cross a mouse genetically engineered to have its senescent cells die (rather than go into that “zombie” state) with a mouse prone to develop skin cancer. “We believe this research will lead to a model to study all types of cancer,” said Campisi. “Our goal is a deeper understanding of the molecular links between aging and cancer. In addition to developing therapies, we are also hoping to identify new markers for early diagnostic tests and risk assessment.” 

The NCI’s Provocative Questions project emerged from discussion among a number of veteran cancer researchers who noticed there were many questions that begged for answers. Some were important but not very obvious, some had been abandoned because there was no way to study or address them, and some were sparked by new discoveries or novel technologies. Over the course of 18 months, NCI settled on 24 questions that, if answered, could lead to significant research advances. For example, one question is aimed at understanding the link between obesity and cancer; another seeks to determine whether improved measurement technologies can be used to better ascertain exposure to cancer risk.

More than 700 researchers applied for funding to research the questions. The Buck’s Campisi is among the fewer than 60 who received awards.