Antibody discovered to lead the fight against bone cancer

Cancer is the second leading cause of death globally, with a range of causes and manifestations. In 2015, 8.8 million people died from cancer, and most people know at least one person who has been affected by this aggressive disease. The battle to find effective treatment options is fierce, demanding a huge amount of money and resources annually - and breakthroughs are unfortunately limited. Excitingly, leading researchers in the US have recently identified a human antibody that could be instrumental in halting the spread of cancers.The majority deaths from cancer are due to metastases, secondary tumours that are formed when cancer cells break away from an existing tumour and enter the bloodstream, travelling around the body and into other organs or bones. When cancer spreads into bones it can cause intense pain, heightened risk of fracture and potentially lethal complications like hypercalcemia - heightened calcium in the bloodstream.

In bone cancers, the normal regeneration of bone by osteoblasts and osteoclasts is interrupted, and these cells can end up producing too much bone or sheltering tumour cells against the effects of chemotherapy. Bone metastases are impossible to operate on and notoriously difficult to treat due to a large range of undesirable side effects and the chance that the cancer can become resistant to treatment options. For this reason, the possibility of development in the treatment of bone metastases is very exciting.

Breast cancer is the most common form of cancer in females, with 55,222 new cases reported in the UK in 2014, and metastasis occurs particularly commonly in these patients. Research into treatment is in more urgent demand than ever, and findings could help to bring down the number of deaths associated with breast cancer.

At New Jersey’s Princeton University, Yibin Kang and his team of researchers are working towards halting the spread of cancerous cells into bone. Their groundbreaking recent study observes how cancerous cells communicate with unaffected cells, causing them to merge and mutate. Rebecca Tang, a member of Kang's team, explains, "Previous work in the lab had shown that a molecule called Jagged1 is a critical part of this crosstalk and makes it easier for breast cancer cells to metastasise to bone.” It’s known that can be tackled by antibodies, so the team focused on identifying a naturally occuring antibody that could successfully block Jagged1.

In a series of experiments including genetically modified mice, Jagged1-containing tumour cells in bone were treated with a mixture of chemotherapy and an antibody called 15D11, and the results were better than could be expected when either treatment was applied on its own. 15D11 specifically targets the molecule Jagged1, destroying the shield formed around the osteoblast and allowing chemotherapy to work successfully again. In one experiment, a tumour was reduced more than a hundred fold. “This is a remarkable response that we have never observed in any of our previous tests of therapeutic agents against bone metastasis in mice,” says Kang.

So what’s the next step in this hopeful development for cancer patients? Kang hopes to bring the research to human patients, which will hopefully be a relatively quick process because the 15D11 antibody is “fully human, having been generated in a humanized mouse." There is plenty of scope for applying the findings to further research on other types of cancer in bones, such as prostate cancer, which is another cancer with a high risk of metastasis. These findings establish 15D11 as a potential therapeutic agent for the prevention or treatment of bone metastasis, and a powerful new ally in the fight against cancer.

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