Bone drugs have anticancer properties

A study led by the Garvan Institute of Medical Research has shown why calcium-binding drugs commonly used to treat people with osteoporosis, or with late-stage cancers that have spread to bone, may also benefit patients with tumours outside the skeleton. Their results have been published in the journal Cancer Discovery.

The drugs, called bisphosphonates, were distributed to women with breast cancer alongside normal treatment for early-stage disease. The clinical trials found that the drugs can confer a ‘survival advantage’ and inhibit cancer spread in some women, although no-one understood why.

The researchers used sophisticated imaging technology called real-time intravital two-photon microscopy to reveal that bisphosphonates attach to tiny calcifications in tumours in mice. These calcium-drug complexes are then devoured by tumour-associated macrophages (TAMs) - immune cells that the cancer hijacks early in its development to conceal its existence.

“We do not yet fully understand how the macrophages revert from being ‘bad cops’ to being ‘good cops’, although it is clear that this immune cell interacts with tumours, and probably changes its function in the presence of bisphosphonates,” said project leader Professor Mike Rogers.

Study co-author Dr Tri Phan added, “Our next step will be to analyse the changes that take place in macrophages, so that we can understand their change in function and effect on cancer cells.”

The researchers have released two video clips of the process - one showing real-time distribution and uptake of bisphosphonate (tagged red) in a breast tumour and the other showing a macrophage devouring a calcium-bisphosphonate complex in a breast tumour. Dr Phan said the macrophages behaved like “little Pacmen … gobbling up the drug”.

   

Once the team realised what was happening in mice, they worked with colleagues at St Vincent’s Hospital in Sydney and obtained a tumour sample from a patient with breast cancer who had undergone surgery. They stained the tissue for calcifications and found them next to and even inside macrophages, indicating that the same process happens in humans.

“This study is potentially transformative for treatment of some cancers, because it is telling us for the first time that drugs we thought acted only in bone can also act within tumours completely outside the skeleton, and have a beneficial effect,” said Professor Rogers.

“We already know this drug is well tolerated in people and provides a survival advantage for some patients with certain cancers when taken early in disease development. This now provides a rationale for using these drugs in a different, and potentially more effective, way in the clinic.”

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