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Bisphosphonates may hold potential for treatment, prevention of some cancers
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Bisphosphonates could potentially be repurposed for the prevention and adjunctive therapy of cancer driven by human epidermal growth factor receptors, according to research published in the Proceedings of the National Academy of Sciences.
Through connectivity mapping, researchers at the Icahn School of Medicine and the Tisch Cancer Institute, both at Mount Sinai, identified human epidermal growth factor receptors (HER) as a potential molecular entity for bisphosphonate action.
“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,” Mone Zaidi, MD, director of the Mount Sinai Bone Program and a member of the Tisch Cancer Institute, said in a press release.
Mone Zaidi
“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,” Zaidi said. “It would be much more efficient than starting drug design from scratch.”
Zaidi, with Tony Yuen, PhD, also of the Tisch Cancer Institute, and colleagues from institutions around the globe used protein thermal shift and cell-free kinase assays, with computational modeling.
Bisphosphonates bind to the kinase domains of HER proteins, preventing abnormal growth signals from passing on; this includes the forms of the protein family making some tumors resistant to leading treatments, according to the release.
Results encompassed four types of tyrosine kinase receptors — HER1, HER2, HER3 and HER4 — that occur on the surfaces of cells, regulating division and proliferation.
Once a bisphosphonate-receptor connectivity map link was digitally detected, the scientists conducted experiments in cancer cell cultures that validated the potential of treating HER-driven cancers with the drugs alone and in conjunction with the approved tyrosine kinase inhibitor erlotinib (Tarceva, OSI Pharmaceuticals), according to the release.
The research was published with a second paper, by several of the same researchers at Mount Sinai and abroad, that examines repurposing of bisphosphonates for the prevention and therapy of non–small cell lung and breast cancer.
“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,” Zaidi said in the release. “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 nontraditional funding source, perhaps the federal government.”
For more information:
Stachnik A. Proc Natl Acad Sci USA. 2014;doi:10.1073/pnas.1421422111.
Yuen T. Proc Natl Acad Sci USA. 2014;doi:10.1073/pnas.1421410111.
Disclosure: The work was supported by grants from the NIH, Italian Space Agency and National Science Foundation of China, and awards from the National Center for Advancing Translational Science through Mount Sinai and Howard Hughes Medical Institute. Some of the researchers are inventors of a pending patent application related to the work described.
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