$2.7 million boosts effort to create the big view of cancer

Many scientists like to discuss how each form of cancer is a distinct disease with its own causes and its own treatments. But researcher Hartmut "Hucky" Land, Ph.D., takes the opposite approach: He is hunting for the most basic rules that all cancers share to make good cells go bad.

His unique, far-reaching effort to understand the disease at its roots poses a huge challenge that is matched only by the potential payoff - findings that could lead to new treatments for not just one but many forms of cancer.

The project has taken a big step forward with a $2.7 million grant from the National Cancer Institute to unravel the gene networks at the heart of colon cancer. The funding will support work for the next five years in the laboratory of Land, who is scientific director of the James P. Wilmot Cancer Center at the University of Rochester Medical Center.

The grant comes on the heels of one of the most important findings Land has made in his three decades as a scientist. Earlier this year in the journal Nature, Land's team demonstrated a promising way to pinpoint the genes that are essential in turning cells from normal to cancerous.

"No matter what type of cancer a person has, a similar program is happening in every cell that becomes cancerous," said Land, who is professor and chair of the Department of Biomedical Genetics. "We're trying to figure out that program and then dismantle or destroy it."

The new funding is focusing on the genes behind colon cancer, which claims approximately 50,000 lives in the United States each year. But researchers predict that the same genes will play important roles in a number of other types of cancer as well. Helping Land unravel the puzzle are Craig Jordan, Ph.D., professor of Medicine and director of translational research at the James P. Wilmot Cancer Center, and Anthony Almudevar, Ph.D., and Peter Salzman, Ph.D., who are both assistant professors in the Department of Biostatistics and Computational Biology.

A cell that makes the journey from normal to cancerous undergoes thousands of modifications. Scientists face the tremendous task of distinguishing between changes that cause the transformation and the changes that simply occur as a result. Land says the task is like sorting out the molecular "drivers" that push a cell to become cancerous vs. the molecular "passengers" that are simply along for the ride.

In the work published earlier this year, his team found a straightforward way to make the distinction. The team found that most of the important genes in the whole genome are much more likely to respond to several mutations in a synergistic way, jumping in activity more than would be expected if the changes caused by any of these mutations separately were simply added together.

The research provides a sought-after prize for scientists trying to decide which genes and proteins to target in the fight against cancer.

"We believe this is a way to identify what we call cancer addiction genes," said Land. "These are the genes that cancer simply must affect to cause the disease."

Land has long set his sights on the broader picture of cancer. Twenty-five years ago, he was among a small group of scientists who discovered that the development of cancer always involves more than one mutation. Since then, he has focused on how genes must cooperate for cancer to occur.

The scene that Land and colleagues encounter when gazing upon a cell that is becoming cancerous rivals that of any extraordinarily complex situation, such as a battlefield. In real life, privates, corporals, colonels, medics, cooks, drivers, bystanders, civilians, and countless others scurry about in what seems like massive chaos to an observer. Land's team is trying to sort out the players on the battlefield of cancer, looking at whether there is order beyond the chaos and identifying the core players in command of cancer's assault on cells.

"Now that we have a way to identify the genes that cancer is addicted to, we're moving to the next step and working out the relationships among them," said Land. "These additional targets dramatically expand our opportunity for intervention to help patients."

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