Innovative Strategy Doubles Chemotherapy Efficacy by Targeting Cancer Adaptation

In a groundbreaking study published on July 22, 2025, in the Proceedings of the National Academy of Sciences, researchers at Northwestern University have unveiled a novel approach that significantly enhances the effectiveness of chemotherapy in treating cancer. This innovative strategy, developed by a team led by Dr. Vadim Backman, utilizes a unique methodology aimed at dismantling cancer cells' adaptive capabilities rather than directly targeting the cells themselves. The findings indicate that the engineered approach has the potential to double the efficacy of standard chemotherapy treatments, particularly in cases of ovarian cancer.

The research focuses on the role of chromatin, the complex of DNA and proteins that forms chromosomes within the cell nucleus, which has been identified as a critical factor in cancer cells' ability to resist treatment. According to Dr. Backman, the chromatin structure allows cancer cells to encode 'memories' of their adaptive responses, enabling them to survive even the most aggressive treatments. "Cancer cells are exceptional at adapting to various forms of therapy, often learning to evade immune responses and resist chemotherapy and radiation," explained Dr. Backman, who is the Sachs Family Professor of Biomedical Engineering and Medicine at Northwestern University.

To combat this adaptability, the researchers employed a computational model to analyze chromatin packing and its influence on cancer cell survival. This model allowed them to predict survival rates of cancer cells prior to treatment. They then screened existing FDA-approved drugs and identified celecoxib, an anti-inflammatory medication, as a candidate capable of modifying chromatin structure to reduce cancer cells' adaptive abilities. This innovative approach led to the formation of a new class of drugs termed Transcriptional Plasticity Regulators (TPRs).

In a series of experiments combining celecoxib with paclitaxel, a common chemotherapy drug, the team observed a significant increase in cancer cell death and a reduction in tumor growth rates in mouse models. "The results indicate that leveraging TPRs in conjunction with traditional chemotherapy could not only enhance treatment efficacy but also allow for lower doses of chemotherapy, potentially minimizing the adverse side effects associated with cancer treatment," stated Rachel Ye, a graduate student in Backman's laboratory.

The implications of this research extend beyond oncology, as Dr. Backman suggests that the principles of chromatin modulation may also hold promise for treating other complex diseases, including neurodegenerative disorders and cardiovascular diseases. The research is supported by multiple grants from the National Institutes of Health and the National Science Foundation, highlighting its significance in advancing cancer treatment methodologies.

As cancer remains a leading cause of mortality worldwide, this innovative approach could revolutionize how physicians treat patients, providing a pathway to more effective, less debilitating therapies. Dr. Backman concludes, "By understanding and reprogramming the chromatin structure, we may be able to restore cellular function and memory, potentially transforming the treatment landscape for various diseases."