Innovator plans to map genome of single cells to paint cancer's big picture

Cancer begins when a single cell goes haywire. Now the keys to understanding that cell's transition to lethal tumor may be found in the unprecedented analysis of single tumor cells.

By isolating, capturing and then analyzing the genome of individual cells, Nicholas Navin, Ph.D., assistant professor in MD Anderson's Department of Genetics, proposes to identify the mutations that allow a primary tumor cell to escape into the bloodstream and then to establish a deadly colony in another organ.

Successfully analyzing differences in active mutations among single cells would help researchers understand, map and eventually block the lethal path to metastasis - the spread of the primary cancer to other organs. Primary tumors are rarely lethal, Navin notes, but their genetic diversity from cell to cell hinders scientists' ability to understand metastasis.

The Damon Runyon Cancer Research Foundation will give Navin the opportunity to try his unique approach. He is the Nadia's Gift Foundation Innovator, one of only seven 2013 Damon Runyon-Rachleff Innovation Awards announced earlier this month.

The foundation announcement notes the innovation awards are for "cancer research by exceptionally creative thinkers with "high-risk/high-reward" ideas who lack sufficient preliminary data to obtain traditional funding." Navin's approach "will have myriad clinical applications, which have prognostic value in predicting invasion, metastasis, survival and response to chemotherapy." Navin agrees his project is high-risk, high-reward because it breaks new ground in the genomic analysis of cancer.

First, he must develop tools to reliably isolate individual cancer cells and identify mutations in all of the genes that encode proteins. Then he will apply single-cell gene sequencing to triple-negative breast cancer, the most lethal form of the disease.

"Most of the tools we have now operate on bulk tumor tissue samples, which include normal supportive cells, or stroma, and immune system cells as well as cancer cells, which have different genetic mutations," Navin said. Analyzing tissue in bulk yields an average genetic profile. "What you miss are the rare cells that may be most malignant," he says.

Identifying these cells is particularly important for those with triple-negative breast cancer, which does not have the three protein targets that make other breast cancers more treatable.

"Triple-negative breast cancer is the most aggressive type, with the lowest survival rates, the most genetic diversity within the tumor and greatest likelihood of spreading," Navin said. "So there's really a dire need to help these patients by developing new therapies to inhibit metastasis."

Additional information: Navin lab MD Anderson news release