Scientists Double Chemotherapy Effectiveness by Targeting Resistance

Scientists at Northwestern University have made significant strides in cancer treatment, demonstrating a method that doubles the effectiveness of chemotherapy for resistant cancer types. By focusing on restoring cellular memory, the researchers have developed a strategy that prevents cancer cells from adapting to evade treatment, a breakthrough that may change how therapies are administered.

The team, led by biomedical engineer Vadim Backman, conducted experiments that showed their approach not only targets cancer cells more effectively but also enhances the efficacy of existing drugs. In mouse models of human ovarian cancer, the new method led to nearly complete eradication of the disease in cellular cultures, showcasing its potential for broader applications in cancer therapy.

Cancer’s ability to survive under aggressive treatment regimens is well-documented. While genetic mutations contribute to resistance, they occur too slowly to explain the rapid adaptability of cancer cells. Backman points out, “Cancer cells are great adapters…They can adapt to almost anything that’s thrown at them.” This adaptability allows them to outlast treatments such as chemotherapy and immunotherapy, leading to longer survival and the acquisition of more mutations.

Central to this research is the role of chromatin, the complex of DNA and proteins that organize genetic material within cells. The way chromatin is structured determines which genes are activated or suppressed, significantly influencing how cells respond to stress and treatment. The researchers found that the three-dimensional arrangement of chromatin can store memories of gene transcription patterns, functioning much like a self-learning system. This memory enables cancer cells to adapt quickly when faced with therapeutic challenges.

Through a combination of imaging, simulations, and in vivo experiments, the research team elucidated how chromatin packing influences cancer cell survival. By altering this packing architecture, they aimed to diminish cancer cells’ adaptive capabilities. Instead of creating new drugs, the researchers screened existing compounds and identified celecoxib, an FDA-approved anti-inflammatory medication, as a candidate that could modify chromatin structure.

Interestingly, celecoxib, commonly prescribed for arthritis and heart conditions, has a side effect that alters chromatin packing. The researchers found that when celecoxib was combined with standard chemotherapy, there was a marked increase in cancer cell mortality. This discovery opens the door to a new class of therapeutic agents known as Transcriptional Plasticity Regulators (TPRs), which could be pivotal in future cancer treatments.

The findings of this research were published in the journal Proceedings of the National Academy of Sciences and are detailed in the paper titled “Leveraging chromatin packing domains to target chemoevasion in vivo.” This innovative approach not only enhances the current understanding of cancer biology but also provides a promising avenue for improving treatment outcomes for patients facing resistant cancers.

As researchers continue to explore the complexities of cancer resistance, the potential for TPRs and similar compounds may offer new hope in the ongoing battle against this formidable disease.