Ferroptosis: An arrow into the metabolic Achilles' heel of recurrent breast cancer

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Breast cancer is the second most common cancer among women in the United States. One in eight women will develop the disease. Typically, patients respond well to initial treatment, which usually includes some combination of surgery, radiation, chemotherapy and hormone treatment.

However, some people, even after being in remission for years, can develop recurrent breast cancer tumors, which are often more aggressive and less responsive to the therapies employed in initial cases.

In a study published in Oncogene, Jen-Tsan Ashley Chi, M.D., Ph.D., associate professor in molecular genetics and microbiology, Chao-Chieh Lin, Ph.D., and team discovered recurrent breast cancer cells’ Achilles heel: their vulnerability to ferroptosis.

Ferroptosis is a type of iron-dependent oxidative cell death which can be triggered when the tumor cells have a shortage in the intake of one type of amino acid, cystine. Cystine is a key factor in neutralizing the oxidative stress in cancer cells.

“The tumor cells evade initial treatment recur by rewiring its signaling pathways and metabolism,” Chi said, “which require much more cystine intake to neutralize its oxidative stress to survive.”

Ferroptosis opens more doors for therapeutic options in treating aggressive, recurrent breast cancer. Chi plans to investigate other cancers as well to see if metastases and recurrent tumors for additional cancer types may also respond to ferroptosis.


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