PUBLIC RELEASE DATE:

1-Dec-2014

Contact: Renatt Brodsky renatt.brodsky@mountsinai.org The Mount Sinai Hospital / Mount Sinai School of Medicine @mountsinainyc

The most commonly used medications for osteoporosis worldwide, bisphosphonates, may also prevent certain kinds of lung, breast and colon cancers, according to two studies led by researchers at the Icahn School of Medicine at Mount Sinai and published today in the Proceedings of the National Academy of Sciences (PNAS).

Bisphosphonates had been associated by past studies with slowed tumor growth in some patients but not others, and the mechanism behind these patterns was unknown. In the studies published today, an international research team showed that bisphosphonates block the abnormal growth signals passed through the human EGF receptors (HER), including the forms of this protein family that make some tumors resistant to leading treatments. The connection between bisphosphonates and HER receptors was detected first in a genetic database analysis and confirmed in studies of human cancer cells and in mice.

"Our study reveals a newfound mechanism that may enable the use of bisphosphonates in the future treatment and prevention of the many lung, breast and colon cancers driven by the HER family of receptors," said lead study author Mone Zaidi, MD, Professor of Medicine and of Structural and Chemical Biology within the Icahn School of Medicine at Mount Sinai, Director of the Mount Sinai Bone Program and a member of the Tisch Cancer Institute at Mount Sinai. "Having already been approved by the FDA as effective at preventing bone loss, and having a long track record of safety, these drugs could be quickly applied to cancer if we can confirm in clinical trials that this drug class also reduces cancer growth in people. It would be much more efficient than starting drug design from scratch."

Of the two newly published PNAS papers, one describes the evidence that bisphosphonates block abnormal growth signals through HER family receptors, while the second examines the potential applications for this new mechanism: cancer prevention, combination with existing treatments, and use against treatment-resistant tumors.

Stop Abnormal Growth

The study results revolved around the human epidermal growth factor receptor (HER/EGFR) family, which consists of four types of transmembrane tyrosine kinase receptors: HER1, HER2, HER3, and HER4. HER family members occur on the surfaces of many cell types and regulate cell division and proliferation, processes closely linked to both normal tissue growth and the abnormal growth seen in cancer.

A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by random genetic changes (somatic mutations) that make HER family receptor tyrosine kinases more active drivers of abnormal growth. About of 30 percent of nonsmall cell cancers (NSCLCs) and 90 percent of colon cancers are driven by small genetic changes in HER1, while 25 percent of breast cancers proceed from genetic changes that result in excessive amounts of HER2.

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Widely used osteoporosis drugs may prevent breast, lung and colon cancers