Discovering Why Some Cancer Cells are Drug Resistant

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Cancer researchers at UC San Francisco have discovered a common gene vulnerability in certain treatment-resistant cancers. This is yet another promising advancement that could lead to better treatment of existing cancers and a new approach to preventing cancer recurrences.

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Understanding drug-resistant cancer cells

For many years, oncologists thought the drug resistance of cancer cells evolved genetically. Doctors thought a few of the cells survived cancer treatment because they had or somehow developed gene mutations to withstand traditional treatments. These remaining cells would then lead to a recurrence of cancer.

In 2010, researchers working at the Massachusetts General Hospital Cancer Center found that some cancer cells may be able to avoid the effects of treatment without any genetic mutations. These small clumps of cells are called "persister cells" and they go into a dormant state, allowing them to survive cancer drugs. The cells awaken later and lead to new cancer growth.

Exploiting persister cell weaknesses

Matthew Hangauer, PhD led the UC San Francisco study. He said persister cancer cells have a mesenchymal-like gene expression signature and rely on the enzyme glutathione peroxidase 4 (GPX4) to survive treatment. Lab tests show that blocking GPX4 can kill the persister cells found in many different cancer types. Researchers hope to soon validate their findings with human patients.

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