Northwestern University Researchers Develop New Approach to Cancer Treatment by Targeting Chromatin Packing

Strategic Insights -

In a breakthrough study published in the Proceedings of the National Academy of Sciences, Northwestern University biomedical engineers have discovered a new approach to cancer treatment that doubles the effectiveness of chemotherapy in animal experiments. Led by Vadim Backman, the team developed a strategy that prevents cancer cells from evolving to withstand treatment by targeting the intricate organization of genetic material, called chromatin. By reprogramming chromatin conformation, the researchers were able to make chemotherapy more effective and potentially reduce the burden of its difficult side effects.

Key Takeaways:

  • The researchers discovered that chromatin packing is critical for cancer cell survival and that altering its architecture can prevent cancer cells from adapting to treatments.
  • The team developed a computational model that uses physics to analyze how chromatin packing influences a cancer cell's odds of survival against chemotherapy.
  • The researchers selected celecoxib, an FDA-approved anti-inflammatory drug, as a candidate that can alter chromatin packing and enhance chemotherapy effectiveness.
  • The combination of celecoxib with standard chemotherapy caused a substantial increase in the number of cancer cells that died in cellular cultures and mouse models of ovarian cancer.
  • The approach has the potential to enable physicians to prescribe lower doses of chemotherapy for patients, reducing the side effects associated with treatment.
  • The researchers believe that modulating chromatin conformation could be a key to treating various complex diseases, including heart disease, neurodegenerative diseases, and more.
  • Cells in the body maintain memory for a long time, but they can also develop spurious memories or lose memories, which can lead to diseases such as cancer and Alzheimer's.

Statistics:

  • The researchers found that the combination of celecoxib with standard chemotherapy doubled the efficacy of treatment in mouse models of ovarian cancer.
  • The team discovered that chromatin packing influences a cancer cell's odds of survival against chemotherapy in a range of 50% to over 90%.
  • Over 700 existing drug compounds were screened to select candidates that could alter chromatin packing.
  • The study was supported by multiple funding sources, including the National Institutes of Health, National Science Foundation, and philanthropic support from various organizations.
  • Each cell in the body has several thousand chromatin domains, which are actual physical elements of transcriptional memory.

Sources:

  • Proceedings of the National Academy of Sciences
  • National Institutes of Health
  • National Science Foundation
  • Lefkovsky Innovation Award
  • Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust
  • Philanthropic support from Rob and Kristen Goldman, David Sachs, and the Christina Carinato Charitable Foundation.