Two recent studies that found bisphosphonates may be a feasible treatment for lung, breast and colon cancers were published this week in the Proceedings of the National Academy of Sciences (PNAS).
Bisphosphonates are commonly used for the treatment of patients with osteoporosis and skeletal metastases. There is some evidence showing that bisphosphonates reduce cancer progression but only in specific cancers, indicating there may exist a mediational determinant in the action of bisphosphonates on tumour cells.
In the first study entitled “Bisphosphonates inactivate human EGFRs to exert antitumor actions”, a team of researchers from the Icahn School of Medicine at Mount Sinai, identified a human epidermal growth factor receptor (EGFR or HER), from the family of tyrosine kinases receptors (RTKs), as a potential factor mediating the action of bisphosphonates on cancer reduction. In this study, the researchers found bisphosphonates bind the kinase domain of HER1/2 and trigger a decrease in downstream signalling, killing lung, breast and colon tumour cells that have a mutant or hyperactivated form of HER1 (one of the four forms of transmembrane tyrosine kinase receptors).
Concerning the results of this study, first author Dr. Mone Zaidi said in a press release, “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”.
In the second study entitled “Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer”, the team showed that targeting HER1 could be a potential therapy for HER-driven cancers. The researchers found that bisphosphonates could be used as an adjunctive therapy to tyrosine kinase inhibitors (TKIs), which include the drugs gefitinib and erlotinib. In this study bisphosphonates were found to bind TKIs within the HER1 kinase domains, which consequently stopped and even reversed cancer cell growth in mice models.
‘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.”, Dr. Zaidi concluded in the press release.