denosumab, already FDA approved for osteoporosis, may block breast tumors
I have written with hope about denosumab in the past. Now more is being revealed regarding its anti-breast cancer effects. SO far it is approved for osteoporosis only, not yet for breast or prostate cancer bone mets
Bone Drug Denosumab (Prolia) May Block Breast Tumors
- The same mechanism that makes Amgen's new bone drug denosumab (Prolia) an effective treatment for osteoporosis may also mean it could help prevent breast cancer, scientists say.
Two papers published online September 29th in Nature report that the key osteoclast differentiation factor RANKL, which helps regulate bone resorption, also has a role in breast cancers induced by endogenous hormones.
The finding suggests that hormone-induced breast cancer could be blocked by denosumab, the first in a new class of drugs that inhibit RANKL.
"Further studies will be needed to prove the principle of our findings," said Dr. Daniel Schramek, who worked on the research with Dr. Josef Penninger at the Institute of Molecular Biotechnology in Vienna. "But we hope that medical trials using denosumab can be started in the near future to test whether the mouse studies can be directly translated to human breast cancer."
Dr. Schramek and Dr. Penninger and their colleagues found that treating mice with medroxyprogesterone acetate (MPA) triggers massive induction of RANKL - which stands for "receptor activator of nuclear factor (NF)-kappa B ligand" -- in mammary-gland epithelial cells. On the other hand, inactivation of the RANKL receptor in these cells prevented them from proliferating and increased their rate of apoptosis.
Furthermore, deleting the RANKL receptor from the mammary epithelial cells "results in a markedly decreased incidence and delayed onset of MPA-driven mammary cancer," the research team reports.
In a second study in Nature, also using mice, scientists at the U.S. biotech giant Amgen found that found that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis. Induced activation of RANKL causes the mammary cells to divide and multiply and fail to die when they should, and the inappropriate proliferation ultimately leads to breast cancer, according to the report.
"The permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium," the authors report.
Blocking the RANKL mechanism not only reduced breast tumor formation but also decreased the spread of cancers to the lungs.
Prolia won approval from European regulators in May and from U.S. regulators in June for treatment of the brittle bone disease. It is now under priority review by the U.S. Food and Drug Administration as a treatment for patients with advanced cancers that have spread to the bones.
Nature. Posted online September 29, 2010
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