Hacking Cancer’s Survival Code

Cancer’s defining trait is its relentless ability to survive — even against attacks from the immune system and harsh medical treatments. 

Northwestern biomedical engineers have developed a first-of-its-kind strategy that prevents cancer cells from evolving to resist therapies. The approach nearly wiped out cancer in lab-grown cells and significantly enhanced chemotherapy’s effectiveness in a mouse model of cancer.  

“Cancer cells are great adapters,” says Vadim Backman, the Sachs Family Professor of Biomedical Engineering and Medicine at the McCormick School of Engineering, where he directs the Center for Physical Genomics and Engineering. “They can adapt to almost anything that’s thrown at them, [including] chemotherapy immunotherapy and radiation. When they resist these treatments, they live longer and acquire mutations.  

“We did not set out to directly kill cancer cells. We wanted to take away their superpower — their inherent ability to adapt, to change and to evade.”  

Backman’s team previously discovered that cancer’s ability to adapt depends on how chromatin — a collection of molecules including DNA, RNA and proteins — is organized within a cell’s nucleus.  

Chromatin self-organizes into “packing domains” — distinct, compact regions of molecular structures that play a crucial role in regulating gene expression. The three-dimensional architecture of chromatin packing allows cells to physically encode memories of gene transcription patterns. A cell’s transcriptional memory dictates how the cell functions, and problems with transcriptional memory can lead to diseases and might even drive aging.  

When chromatin packing is disordered, a cell demonstrates an increased ability to adapt in order to resist treatments.  

“Many impactful diseases of the 21st century are, to a large extent, related to cell memory — cells forget what they should be doing,” Backman says. “Cells maintain memory for a long time, but they can also develop spurious memories or lose memories. Cancer cells take that to the extreme. I think what we have found here is the source code of cell memory.”  

The team built a physics-based computational model that analyzes chromatin organization to predict whether cancer cells will survive chemotherapy treatment. When tested across multiple cancers and drug classes, the model accurately forecast cell survival before treatment began.

Next, Backman and his team sought to change the organization of chromatin to explore how it might affect cancer’s survival. They screened various existing drugs for candidates that could reshape chromatin inside the nucleus. Ultimately, they selected celecoxib, an FDA-approved anti-inflammatory drug that happens to alter chromatin as a side effect.  

Backman’s team tested celecoxib’s effectiveness by combining it with a common chemotherapy drug in a mouse model of ovarian cancer. The combined treatment reduced the cancer cells’ adaptation rates and inhibited tumor growth — outperforming the chemotherapy drug by itself.  

By making chemotherapy more effective, the strategy could enable physicians to prescribe treatments that include lower doses of chemotherapy for patients.  

“Chemotherapy can be so hard on the body,” says Backman, who is also professor of medicine and biochemistry and molecular genetics at the Feinberg School of Medicine. “A lot of patients, quite understandably, sometimes choose to forego chemotherapy. They don’t want to suffer in order to live a few months longer. Maybe reducing that suffering would change the equation.”  

Backman says celecoxib and similar drugs could become a new class of compounds that can prevent cancer cells’ adaptive abilities. He says modulating chromatin organization might be the key to treating various complex diseases, including neurodegenerative diseases, heart disease and more.