It is crucial that we understand how a Giant Cell Tumour of the Bone (GCTB) develops and progresses if research is to move forward and new treatment advances are to be established for this tumour type.

What we know about the development of a GCTB:

The main components of a GCTB are ‘spindle-like stromal cells’. When these cells are activated they express and release a wide range of molecules that are responsible for the formation of giant cells (the main cell making up a GCTB). The molecules produced by the ‘spindle-like stromal cells’ include VEGF, MMP-9 and RANKL - which are all involved in different aspects of cell signalling to encourage the tumour cells characteristics, development and growth.

Studies have shown that the molecules VEGF and MMP-9 are involved in bone destruction and increasing the likelihood of the tumour returning at a later date – which are two crucial aspects of a GCTB.

Can the factor RANKL be targeted to treat GCTB?

Research regarding another factor, RANKL, has shown great research promise. RANKL promotes bone destruction when it binds specifically to a receptor known as RANK, which presents on the surface of the giant cells.

Research currently being funded by The Bone Cancer Research Trust, carried out by Professor Anthanasou, is investigating if inhibiting RANKL in Ewing sarcoma and osteosarcoma may relieve patient’s symptoms of bone pain and reduce the growth of these tumours. Read more about this research here.

Research into RANKL recently lead to the development of a targeted therapy known as ‘Denosumab’ - which was licensed for use in GCTB treatment in September 2014. Multiple clinical trials analysing the safety and efficiency of Denosumab in GCTB patients were extremely positive. The majority of patients involved in the study experienced an elimination of the giant cells, a reduction in bone pain and a positive clinical benefit which lowered the requirement for patients to undergo invasive surgical procedures. Unfortunately, patients also described side-effects of Denosumab - including nausea, headaches and fatigue - and so the long-term aspect of Denosumab is still under investigation.

Future research into the treatment of GCTB?

Further improving our knowledge of GCTB development and progression, in the same manner that RANKL was investigated, will hopefully lead to additional treatment advances for this non-cancerous tumour of the bone. Investigation into the various other factors that are secreted by ‘spindle-like stromal cells’ is ongoing, and over 20 drug compounds targeting these factors are currently being tested for various others diseases. In the near future, these compounds can hopefully be investigated specifically in GCTB and open doors to new treatment innovations that may be used as an extra line of treatment, or as a combination therapy alongside Denosumab.

For more information on Giant Cell Tumour of the Bone and how it is diagnosed and treated, please see our information page on this tumour type here.