Bisphosphonates May Prevent Breast Cancer Through HER Proteins

Bisphosphonates May Prevent Breast Cancer Through HER Proteins

shutterstock_154017506Researchers have found bisphosphonates may no longer be used solely for osteoporosis treatment. Mone Zaidi, MD, of Mount Sinai, recently published two articles identifying bisphosphonates as cancer preventers in the cases of breast, lung, and colon cancers.

“Our study reveals a newfound mechanism tat may enable the use of bisphophonates in the future treatment and prevention of the many lung, breast, and colon cancers driven by the human endothelial growth factor receptors (HER) family of receptors,” said Dr. Zaidi, in a news release from Mount Sinai.

The studies, “Repurposing of Bisphosphonates for the Prevention and Therapy of Nonsmall Cell Lung and Breast Cancer,” and “Bisphosphonates Inactivate Human EGFRs to Exert Antitumor Actions,” were published in the Proceedings of the National Academy of Sciences (PNAS). During experimentation, the research team discovered bisphosphonates bind to HER proteins on the outside of cancer cells and inhibit the passage of growth signals, leading to tumor cell death.

Although a number of HER protein inhibitors exist (such as Herceptin, Tarceva, and Iressa), bisphosphonates are special because they inhibit HER activity even when mutations in the proteins are present. This prevents primary therapy resistance to bisphosphonates, a problem that plagues existing HER inhibitors.

The work was motivated by the observation that bisphosphonate users tend to have a lower occurrence of several cancers. The team used a Connectivity Map of genes that are up- and down-regulated with bisphosphonate use and discovered HER receptor genes were among them. Applying bisphosphonates to cancer cells suggested a therapeutic benefit, and a mouse model of cancer was prevented with bisphosphonate dosing.

The authors believe it is important to investigate bisphosphonate use in cancer patients, as a variety of human cancers express mutated HER proteins. Thirty percent of non-small cell cancers, 90% of colon cancers, and 25% of breast cancers are driven by HER mutations.

“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,” said Dr. Zaidi. “It would be much more efficient than starting drug design from scratch.”

Although this makes theoretical sense, the logistics of using bisphosphonates as a cancer therapy may not pan out as easily as hoped. “While this finding is exciting, there is no business model for conducting the costly clinical trials that would be needed to repurpose bisphosphonates for cancer,” noted Dr. Zaidi. “Pharmaceutical companies are unlikely to pay for research to develop generic drugs where there is no chance of patent protection or profit, so we will be looking for a non-traditional funding source, perhaps the federal government.”