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Gene hope for children's bone cancer treatment

Tuesday July 14th 2020

New genetic discoveries could lead to improved treatments for children with bone cancer – and save more lives.

A study by the University of East Anglia and University of Manchester has identified a set of genes that promote the spread of bone cancer to the lungs in patients. When the genes were tested in mice models with engineered human bone cancer cells, the cancer was unable to spread to the lungs of those lacking the key genes. The findings are published in Oncogene.

The researchers, led by Dr Darrell Green, of UEA’s Norwich Medical School, and Dr Katie Finegan from the University of Manchester, investigated osteosarcoma, the most common type of primary bone cancer whose genetic drivers are TP53 and RB1 structural variants.

Little is known about what drives its spread to other parts of the body, so the team developed new technology to isolate circulating tumour cells in patients’ blood.

Dr Green said primary bone cancer can rapidly spread to other parts of the body, making it the most problematic aspect because it is difficult to treat once it has spread.

Existing treatment options are gruelling, with outdated chemotherapy cocktails and limb amputation, but the five-year survival rate is 42% mainly because of how rapidly bone cancer spreads to the lungs.

After profiling tumours, circulating tumour cells (CTCs) and metastatic tumours from patient donors, the researchers identified MMP9 as a potential driver for metastasis, which is already well-known but it quickly becomes resistant to treatment.

The UEA researchers worked with a team at the University of Manchester, which was working on MAPK7, the proposed master regulator of MMP9, in several cancers using mouse models including osteosarcoma.

Together, they engineered human osteosarcoma cells containing a silenced version of MAPK7 and found when these cells were put into mice, the primary tumour grew much more slowly and did not spread to the lungs.

“If these findings are effective in clinical trials, it would no doubt save lives and improve quality of life because the treatment should be much kinder, compared to the gruelling chemotherapy and life changing limb amputation that patients receive today,” said Dr Green.

Senior author Dr Katherine Finegan, from the University of Manchester, added: “It has been great to work together with Darrell and the team at UEA. Using their genetic insights from patient material, we were able to validate their work in models of primary bone cancer. As a result, we have highlighted a potential new way to treat metastatic bone cancer by targeting a key protein that promotes metastases: MAPK7.

"This work has uncovered a novel treatment option for osteosarcoma, something we have not had for the last 40 years.”

Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer. Oncogene 13 July 2020

Tags: Cancer | Child Health | Genetics | UK News

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