Video: Bone drug seeks out calcium in breast tumours
A chemical originally used to clean pipes, and widely prescribed as a drug for osteoporosis, could also be breast cancer’s nemesis.
Bisphosphonates are a class of chemicals that have a remarkable ability to bind to calcium. That made them a great way to clear out calcified water pipes but more recently they have become a safe and effective treatment for osteoporosis. Just as in pipes, they bind to the calcium in bones, where they’re gobbled up by white blood cells called macrophages which eat up old bone cells so they can be replaced with new ones.
But bisphosphonate is poisonous to macrophages, and kills a proportion of them, slowing the turnover of bone cells – which allows those with osteoporosis to increase their overall bone density.
The drugs have also come to be used to treat late-stage cancer that has spread to the bone. Initially used to protect against side-effects such as fractures, there is also some evidence that taking the drug extends the lives of women with breast cancer. But how does a bone drug act on soft breast tissue?
Inside many breast tumours are tiny granules of calcium. We don’t really understand why they are there but they appear to be associated with more aggressive forms of the disease.
To see if bisphosphates are reacting with the breast calcium, Mike Rogers from the Garvan Institute in Sydney, Australia, and colleagues tagged bisphosphonate molecules with a chemical that glows under a microscope. They gave the drugs to mice bred to have breast cancer and recorded what happened. “I clearly remember the moment we first saw macrophages behaving like little Pac-Men and gobbling up the drug. It was astounding,” says team member Tri Phan.
In the imaging videos, the bisphosphonates can be seen leaking from the veins in the tumour and binding to the calcifications. Once that happens, they are suddenly engulfed by the macrophages and consumed.
Next, the team tested the chemical on a patient. They gave the glowing version of the drug to a woman about to have her primary breast tumour surgically removed. Analysis of the tumour showed that it also been infiltrated by macrophages.
This is important as one of the reasons tumour cells are so pernicious is that they are able to hide from the body’s immune system, by hijacking macrophages. Rogers thinks the bisphosphonates in tumour cells somehow change how macrophages behave – those that had been co-opted by the cancer to hide the tumour suddenly switch sides and attack the cancer, gobbling it up.
The team is now working on showing exactly what changes the bisphosphonates cause in the macrophages, something which could help us understand exactly how cancer is able to evade the immune system. And that could lead to new and better drugs.
“It’s possible that this is part of a new wave of drug treatments that are actually designed to address the immune defect,” says Phan.
Robert Coleman from the University of Sheffield, UK, says we had assumed that bisphosphonates simply wouldn’t get into tumours other than bone cancers at any concentration that could make a difference.
“This exciting paper presents a potential mechanism by which bisphosphonates could get to the breast in reasonable quantities,” Coleman says.
Journal reference: Cancer Discovery, in press
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