Chondrosarcoma affects men more than women (ratio 1.5:1). It is also known that women have improved survival, compared to men of similar age. This effect diminishes after the age of menopause, suggesting that oestrogen could have a protective effect in chondrosarcoma.
In 2020 we awarded our first Ideas Grant focused on chondrosarcoma research, to a collaborative project between the University of Sheffield, the Royal Orthopaedic Hospital in Birmingham and the University of East Anglia. With promising preliminary results from this grant, further funding to investigate the biological mechanisms by which these effect take place and its potential therapeutic opportunity was awarded in 2023.
The team, led by Professor Alison Gartland at the University of Sheffield, aimed to answer the question: “Does the hormone oestrogen have a protective effect in chondrosarcoma?”
What were the aims of this research project?
The project set out to test the effect of oestrogen on human chondrosarcoma cell growth and migration and investigate the effects of oestrogen on chondrosarcoma tumour growth and progression in a patient-derived xenograft (PDX) model of human chondrosarcoma.
What were the results of this project?
Through this Idea Grant, Professor Gartland and her team have taken earlier research suggesting a link between oestrogen and chondrosarcoma an important step further.
Their results provide evidence that oestrogen does indeed have a protective effect in chondrosarcoma, with the potential to prevent further spread and progression.
In addition, the successful development of a model of human chondrosarcoma, using human chondrosarcoma cells (a so called ‘patient derived xenograft model’) is a significant step forwards for future chondrosarcoma research. Tumours derived from this model are now undergoing a type of analysis (so called ‘RNA sequencing’) to compare, at a genetic level, the effects of low vs high circulating oestrogen.
How could the results of this project improve treatment options for chondrosarcoma patients?
Although still preliminary, combined, this data suggests that the oestrogen signalling pathway may represent a potential target for the treatment of chondrosarcoma, particularly in cases where the tumour cannot be surgically removed due to its size or location (‘irresectable’), or where cancer cells have spread to other parts of the body. If so, clinically approved Hormone Replacement Therapy (HRT), used to treat menopausal symptoms, could be repurposed as a targeted treatment for patients diagnosed with chondrosarcoma.
A crucial gap remains in terms of our understanding of the exact underlying mechanisms driving the effects of oestrogen on chondrosarcoma cells. On the basis of these vital early findings, Professor Gartland and her team have been awarded additional BCRT funding to conduct further, in-depth research. They aim to ascertain whether this protective effective can be harnessed as a targeted, pre-approved and readily available treatment for patients, translating these important findings from the laboratory to the clinical setting. You can read more about this further research here.
This project is made possible by a a generous donation by the Albert Gubay Foundation to the Bone Cancer Research Trust.