City of Hope scientists discover pathway that allows cancer to bypass oncology treatments

DUARTE, Calif. — Researchers at City of Hope, a world-renowned cancer research and treatment organization, have identified a pathway that explains how mutated cancer cells can continue to replicate and become resistant to oncology therapies.

Using whole genome sequencing technology, the scientists discovered a new mechanism for how genetically defective cells mutate to survive stressful situations, such as drug treatment. Understanding this resistance mechanism moves researchers one step closer to developing new strategies to prevent cancer development or to delay and overcome resistance to cancer drugs.

“Targeted cancer therapies have transformed cancer care and prolonged patient lives, but many patients eventually develop resistance to their lifesaving treatments. Our basic research hints at how we might one day be able to increase survival by delaying or even preventing the development of cancer drug resistance,” said Binghui Shen, Ph.D., professor and chair of the Department of Cancer Genetics and Epigenetics at Beckman Research Institute of City of Hope.

Shen has been conducting research on the fundamental mechanisms of DNA replication and the key enzyme called flap endonuclease 1 for the past 25 years at City of Hope. This finding, Shen said, is a milestone moment.

The study, published on Dec. 3 in the journal Science, was conducted in yeast, mouse and human leukemia models. As a next step, Shen’s team will see if they can replicate the discovery in more varied human cancer cells and establish regimens to overcome cancer drug resistance.

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The study was supported by the National Institutes of Health (R01 CA073764, R01 CA085344 and R50 CA211397).

About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nation’s “Best Hospitals” in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHope^TM, a subsidiary launched in 2019, serves employers and their health care partners by providing access to NCI-designated cancer center expertise. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.