University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

Mapping Genetic Diversity of Lung Tumors Over Time May Lead to More Effective Therapies

By Jason Alvarez | UCSF.edu | September 3, 2020

Mapping Genetic Diversity of Lung Tumors Over Time May Lead to More Effective Therapies

Lung cancer cells invade surrounding tissues and start to spread. Image courtesy of the National Cancer Institute

A malignant tumor is a bustling metropolis populated by many different kinds of cancer cells. This cellular diversity, however, is what makes cancer so difficult to treat, as each type of cell in a tumor responds differently – and sometimes not at all – to cancer therapies. This is especially true for lung cancer, which often responds to an initial course of treatment, only to remerge after becoming drug-resistant, making it the deadliest form of cancer worldwide.

Trever Bivona

Trever Bivona, MD, PhD;

A better understanding of the diversity that exists within a lung tumor would likely lead to more effective treatments. Today, clinicians generally rely on tests that generate genetic profiles of biopsied tumors in bulk rather than one cell at a time. Unfortunately, this usually fails to capture the full extent of cellular diversity within tumors and ends up obscuring clinically significant information. This has led scientists to search for ways to assemble a census of the many types of cells that comprise a malignant tumor. Even better would be a more complete picture of how these cell populations evolve during the course of treatment. However, figuring out exactly how to conduct this survey has proven to be a major technical barrier for scientists.

But this hurdle, once thought to be nearly insurmountable, was recently cleared by a research team led by UC San Francisco and Chan Zuckerberg Biohub scientists. The researchers figured out how to assemble genetic profiles of individual lung cancer cells obtained from patients at different times during the course of their treatment. In doing so, they revealed a vast cornucopia of cellular diversity in both lung tumors and the tissue surrounding the tumor as they evolved during the course of treatment – clinically significant information that had previously eluded scientists. The findings are detailed in a paper published Aug. 20 in the journal Cell.

“This study is among the first of its kind,” said Trever Bivona, MD, PhD, professor of medicine and senior author of the study. “We observed features of lung cancer cells and the tumor microenvironment that no one had seen before. This gave us a window into the evolution of individual cells within the tumor’s ecosystem.”

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