With high-risk, high-reward investment, UW-Madison researcher seeks to thwart cancer resistance to treatment


UW – Madison Professor of Human Oncology Shuang (George) Zhao studies how cancers become resistant to treatment. To do this, he received a high-risk, high-reward grant from the National Institutes of Health. Photo: Bryce Richter

MADISON – With funding from a National Institutes of Health 2021 High Risk, High Reward New Innovator Award, Shuang (George) Zhao, professor of human oncology at the University of Wisconsin-Madison, hopes to better understand why and how some cancers become resistant to treatment.

Cancer is one of the leading causes of death in the United States, and most of these deaths are the result of a patient’s tumor becoming resistant to available treatments. Similar to antibiotic resistance in which mutant bacteria that survive antibacterial drugs have a competitive advantage, only a few surviving human cancer cells with random genetic mutations that escape treatment can repopulate a tumor and make the disease worse.

The key to understanding this resistance is being able to compare how the molecular characteristics of a person’s tumor cells change over time, says Zhao, who joined UW-Madison faculty less than two years ago. However, current approaches used to obtain tumor samples for sequencing are limited to capturing a single point in time.

“What we’re not so good about right now is looking before and after treatment to understand what changes and how cancer cells evolve in response to treatment and how they might develop resistance to treatment,” Zhao explains. “So the goal of our grant project is to really characterize how resistance develops over time across cancer types.”

An approach called liquid biopsy offers an alternative to invasive tissue biopsies to obtain tumor samples for study. It allows researchers to obtain data on tumor cells circulating in the blood by repeatedly testing blood samples before, during and after treatment. The bulk of the newly funded efforts will go to sequencing the genetic material of samples (DNA and RNA) and performing computer analyzes to detect new mutations in tumor cells.

This will allow researchers to map changes in individual tumors that have become resistant and to discern possible common mechanisms of resistance across multiple tumors.

“You can’t optimally treat a disease until you really understand what’s going on at the molecular level,” says Zhao, who has a doctorate in medicine and training in radiation oncology. “It is an open question whether each person’s cancer has a unique alteration, or if there are common shared mechanisms that explain resistance across tumors. “

The team led by UW-Madison has successfully completed some of their preliminary work on prostate cancer. With a grant for innovative work, which might have been riskier to fund through the traditional peer review process, Zhao’s research groups can continue their research by collecting and sequencing more samples. on different types of cancer.

The payoff could be rapid advances in patient care options tailored to thwart their cancer’s resistance to treatment. Being able to understand why and how cancer cells develop resistance is essential so that researchers and doctors are not shooting in the dark in a race against time. If a doctor knows that a treatment option is one that the cancer will resist, they can try different, more effective options sooner before the patient becomes sicker, Zhao says.

“With more resources, this will really jumpstart our efforts on a number of different types of cancer,” he adds. “As a doctor, I see these patients in my clinic every day and always wish we had more to offer them. I hope that our work can significantly improve the treatments we offer to our patients. “

Zhao is one of 106 researchers nationwide to have received an NIH grant for high-risk, high-yield research this year; 64 of the grants are New Innovator Awards. The scholarships offer $ 1.5 million for unusually innovative research carried out by early-career researchers. The program helps support research proposals with high potential for success and advancement, but which may also have less guarantees than other projects.

Read more in this press release from the NIH.


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