Biomedical engineering associate professor Amy Brock is creating a model to defeat chemotherapy resistance.

Brock’s research focuses on developing models for tumors and cancer growth based on the idea of heterogeneity, which means all cells in a tumor will not react to therapeutics in the same way.

“There are going to be subpopulations of cells that respond more sensitively or less sensitively,” Brock said. 

Brock said her model provides a better fundamental understanding of the growth of cancer and creates a way to treat patients more effectively.

Studies have shown that chemotherapy fails to cure most patients in advanced stages of cancer because some cells develop resistances to the chemotherapy itself. When a tumor is treated with a high dose of chemotherapy, the drug stresses the cell population, causing some cells to become resistant and promote processes that try to push chemotherapy drugs out of the body. 

Treatment is further complicated because the cells develop this resistance at different times, Brock said.

She said the effect of chemotherapy on cancer cells can be compared to bombs used during a war.

“Don’t try to carpet bomb cancer cells and create a stress response, which is worse,” she said. 

Brock said the stress responses are the “insurgents” of this war; they become much more difficult to fight as doses of chemotherapy increase. Acquired chemotherapy resistance poses a risk to cancer treatment when the higher doses of chemotherapy become lethal.

To solve this, Brock’s lab created a mathematical model that evaluates the growth of multiple tumor cell populations after chemotherapy and then categorizes these cells into states to more accurately measure the effects of the drugs. 

Kaitlyn Johnson, a first-year graduate student working with Brock, said by using this generalized model, clinicians could adapt their treatments to affect the cancer cells in a personalized manner.

“We try to understand the entire process, and with the new tools of bioinformatics, we can use the computational power and model what we can measure,” Johnson said. “We are not probing a certain biological mechanism at first, (instead we are asking) how does this cell population respond to drug over time and fit into different models.”

One of the models the lab developed is a multi-state model in which cells transformed the proportions of the tumor cells into two different states, one being resistant to chemotherapy and the other sensitive to it. Johnson said the cell state is defined as a response to therapy. 

“Those states we are not defining biologically, and we don’t know how they are becoming resistant,” Johnson said.

Grant Howard, another graduate student working with Brock, said future research will focus on determining the differences between the two cell states. The next step would be to separate the cancerous cells of different states and try to find the genes causing the resistance to chemotherapy, he said. Through regulating gene expression, researchers could control these different cell states. 

Brock said the future of cancer lies in learning not to completely destroy cells, but instead to manage cancer in the same way as other chronic diseases, such as diabetes.

“We are all walking around with chronic cancers that our body maintains and (that) remain dormant,” Brock said.

The Brock lab also hopes to use specialized equations to study how cancer cells taken specifically from a patient progress in a lab setting — this helps to avoid individual chemotherapy resistance. Brock said learning from cancer is an important resource and that by studying cancer, we can learn infinitely more about the mechanisms that rule our body.