In a novel approach to cancer treatment, biomedical engineers at Northwestern University have doubled the effectiveness of chemotherapy in animal experiments. The strategy does not directly attack cancer but prevents cells from adapting to withstand treatment, thereby enhancing the efficacy of existing drugs.
The study, led by Vadim Backman, was published in the Proceedings of the National Academy of Sciences. It demonstrated significant improvements in chemotherapy's effectiveness against ovarian cancer in mouse models.
“Cancer cells are great adapters,” said Backman. “They can adapt to almost anything that’s thrown at them. First, they learn to evade the immune system. Then, they learn how to adapt to 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 — removing their inherent abilities to adapt, to change and to evade.”
The research focused on chromatin's role in cancer survival—chromatin being a complex structure within cells that dictates which genes are suppressed or expressed. By modifying this organization using an FDA-approved drug called celecoxib, researchers were able to prevent cancer cells from adapting and resisting treatment.
Igal Szleifer commented on this process: “Our genomes are primed to adapt to even new environments like chemotherapies or immunotherapies by using this physical-computing architecture.” Dr. Luay Almassalha added: “By now understanding the physical rules, we’re increasingly finding that just like DNA sequence can be edited to treat diseases, we can edit the physical space.”
The combination of paclitaxel (a common chemotherapy drug) with celecoxib showed promising results in mouse models of ovarian cancer by reducing adaptation rates and improving tumor growth inhibition compared with paclitaxel alone.
“This study opens up novel therapeutic avenues,” said Rachel Ye from Backman’s laboratory.
Backman envisions future applications for other complex diseases beyond cancer by reprogramming chromatin conformation.
“In many diseases, cells forget what they should be doing,” he said. “Many impactful diseases of the 21st century are related largely due cell memory.”