At the Institute of Molecular Biotechnology (IMBA) in Austria, 13 independent groups work on various research topics in genetics and biomedicine. One of the key focus areas of Josef Penninger, scientific director of IMBA, is the various functions of the membrane protein RANKL – from its discovery, to the development of a new drug, which is now prescribed to thousands of patients every year.
Penninger was the first to find genetic evidence that RANKL is the master regulator of adequate bone metabolism by activating osteoclasts, which are critically involved in bone resorption. Overexpression of RANKL is implicated in a variety of degenerative bone diseases such as osteoporosis. RANKL is also known for acting on breast, prostate and skin cancer cells through the RANK receptor.
Penninger’s lab determined that RANKL is essential in controlling the growth of cells that form a lactating mammary gland in pregnancy. Later, the scientists showed that RANKL was the missing link explaining how sex hormones drive breast cancer. A synthetic progesterone, frequently used in hormone replacement therapy and hormonal contraception, was identified to be able to switch on the activity of RANKL within breast cells, causing them to divide and multiply and preventing them from dying when they should. Moreover, stem cells in the breast become able to renew themselves, ultimately resulting in breast cancer.
The osteoclast differentiation factors RANKL/RANK control development of progestin-driven mammary cancer. The illustration above shows the tight link between breast cancer and bone explaining breast cancer metastasis to the bone, cancer-related bone destruction/fractures but also the finding that the osteoclast factor RANKL causes hormone-driven primary breast cancer. (copyright: IMBA)
Today, a monoclonal antibody, Denosumab, that blocks RANKL has been approved in the US and the EU for the treatment of osteoporosis, treatment-induced bone loss, bone metastases, and giant cell tumor of bone.
Josef Penninger will be speaking on the success story of RANKL – From Molecular Medicine to Patient – at 5.05pm on 12th April 2016 at BioProcess International European Summit in Vienna. See the full agenda and register here.