Scientists Disrupt Cancer’s Defense Mechanism, Boosting Chemo Efficacy

Novel Approach Targets Cellular Adaptability, Not Just Tumors

A groundbreaking strategy from Northwestern University engineers has demonstrated the potential to significantly enhance chemotherapy’s power by preventing cancer cells from adapting and resisting treatment, a key factor in treatment failure.

Unlocking Chemo’s Full Potential

Researchers have discovered a way to neutralize cancer’s remarkable ability to evolve and withstand therapies. This new method focuses on the internal scaffolding of cancer cells, known as chromatin, which governs gene expression and cellular responses to stress. By subtly altering chromatin’s physical structure, scientists believe they can disarm cancer’s adaptive superpowers, making existing chemotherapy drugs far more effective.

This innovative approach achieved near-complete eradication of cancer in laboratory cell cultures. In animal trials involving human ovarian cancer models, the combination therapy dramatically improved the outcomes compared to chemotherapy alone.

New approach to cancer treatment could double chemotherapy effectiveness. Northwestern University engineers found a way to prevent cancer cells from adapting and resisting treatment, making them easier to target with existing drugs. https://t.co/101f4c8VzX #CancerResearch #Chemotherapy #Science

— News Medical (@news_medical) July 22, 2022

“Cancer cells are great adapters. They can adapt to almost anything that’s thrown at them… 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.”

—Vadim Backman, Lead Study Author and Professor at Northwestern University

The findings, published in the Proceedings of the National Academy of Sciences, suggest that rather than developing new, potent drugs, the focus can shift to optimizing the delivery and efficacy of current treatments by inhibiting cancer’s resilience. This could lead to less toxic treatment regimens and improved patient quality of life.

Chromatin: The Key to Cancer’s Tenacity

Cancer’s persistent survival, even when faced with aggressive treatments, has long puzzled scientists. While genetic mutations play a role, they don’t fully explain the rapid adaptive responses observed. Researchers led by **Vadim Backman** identified the intricate organization of DNA and proteins within the cell nucleus, known as chromatin, as the critical factor. This complex structure not only controls gene activity but also acts as a cellular memory system, enabling cells to adapt to changing environments and stresses.

When this chromatin architecture becomes disordered, cancer cells gain increased “plasticity,” allowing them to quickly develop resistance to therapies like chemotherapy. The precise 3D arrangement of chromatin stores “transcriptional memory,” guiding cellular function and adaptation.

Reprogramming Cell Memory to Enhance Treatment

The Northwestern team developed a computational model to analyze how chromatin packing influences cancer cell survival. Their research pinpointed celecoxib, an existing anti-inflammatory medication, as a compound capable of modulating chromatin structure and reducing cellular plasticity. By combining celecoxib with standard chemotherapy agents, the researchers observed a significant increase in cancer cell death.

In preclinical trials, the combination of paclitaxel (a common chemotherapy) with celecoxib in mice with ovarian cancer significantly slowed tumor growth compared to paclitaxel alone. “It doubled the efficacy,” **Backman** stated, highlighting the substantial benefit of this combined approach.

The ability to make chemotherapy more effective could also allow for lower, more tolerable doses, potentially alleviating the severe side effects that often lead patients to discontinue treatment. For instance, in 2023, the American Cancer Society reported that over 1.9 million new cancer cases were diagnosed in the U.S. alone, underscoring the immense need for more effective and less burdensome treatments (American Cancer Society).

Future Applications Beyond Cancer

While initially focused on cancer, **Backman** believes that modulating chromatin conformation could offer therapeutic benefits for a range of complex diseases, including neurodegenerative conditions and heart disease. Many debilitating illnesses may stem from cells losing their correct functional “memories,” leading to loss of function or disease development. Restoring these cellular memories through chromatin reprogramming could offer a pathway to recovery.

“In many diseases, cells forget what they should be doing,” **Backman** explained. “Many impactful diseases of the 21st century are, to a large extent, related to cell memory.” He likens the computational processes within each cell’s chromatin to an early computer, emphasizing its capacity for storing and potentially altering cellular memory. This discovery could unlock a new era of “source code” manipulation for treating a variety of human ailments.