THE ESSENTIAL
- By inhibiting the regulator of a potential metastasis factor, researchers from the Universities of East Anglia and Manchester have managed to slow the spread of metastases from primary bone cancer.
- This discovery could, in time, lead to a milder treatment than chemotherapy to treat osteosarcoma.
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Sixth cancer most common in children under 15 with around 52,000 new cases registered each year worldwide, primary bone cancer is a rare cancer but unfortunately often fatal: its five-year survival rate is indeed estimated at 42%.
In question: its tendency to metastasize, in particular towards other organs, in particular the lungs. Children who suffer from it must then endure exhausting and painful treatments, which range from chemotherapy to amputation.
“About a quarter of patients have cancer that has already spread by the time they are diagnosed. About half of patients with apparently localized disease relapse, the spread of cancer being detected later. These figures have been stagnant for more than four decades without any significant breakthrough in treatment, “says Dr. Darrell Green of the Norwich medical school at the University of East Anglia.
Identify the factors of development of metastases
With Dr. Katie Finegan of the University of Manchester, Dr. Green is behind a discovery that could revolutionize treatments for children with osteosarcoma, the most common type of primary bone cancer. While the genetic factors that cause osteosarcoma are well known (structural variants TP53 and RB1), those promoting its spread to other parts of the body have hitherto remained unknown.
The research team thus succeeded in isolating circulating tumor cells (CTC) and metastatic tumors from the blood of patients. “These cells are essential for scientific study because they effectively perform the metastatic process. It was extremely difficult because there is only one such cell per billion normal blood cells – it took more than a year to develop it but we cracked it, “says Dr. Green.
The scientists finally identified a potential factor for metastasis: the MMP9 factor. Well known in the field of cancer, it has hitherto been considered “non-drug” because the cancer quickly becomes resistant to treatment or finds a way to escape the target.
Silencing the MMP9 regulator
The researchers’ objective was therefore to find the “main regulator” of the factor MMP9 to act on it. They then teamed up with scientists from the University of Manchester who were working on the main regulator of MMP9 – MAPK7 – in several cancers using mouse models, including osteosarcoma. Together, they then designed human osteosarcoma cells to contain a silent version of MAPK7.
They discovered that when these cells were put into mice, the primary tumor grew much more slowly. More importantly, it did not spread to the lungs, even when the tumors were left to grow for a long time.
“Deeper still, our study shows that silencing MAPK7 stopped metastasis because this gene pathway hijacked a particular part of the immune system that was causing the spread,” says Dr. Green. “This is really important because not only do we now have a genetic pathway associated with metastasis, but we know that eliminating that genetic pathway actually stops the spread of cancer in a living animal. And we also know how and why it happens – by hijacking the immune system. “
Now the next step is to turn this discovery into treatment. “If these results are effective in clinical trials, it would likely save lives and improve quality of life, as treatment should be much milder compared to exhausting chemotherapy and limb amputation. are changing the lives that patients receive today. “
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