A new stem-cell-based therapy could eliminate metastatic cells from the brain that develop from lung, breast or skin cancers, researchers at Harvard Stem Cell Institute (HSCI) says.
“Metastatic brain tumours – often from lung, breast or skin cancers – are the most commonly observed tumours within the brain and account for about 30% of advanced breast cancer metastases,” says Khalid Shah, an HSCI Principal Faculty member who led the study.
“Our results are the first to provide insight into ways of targeting brain metastases with stem-cell-directed molecules that specifically induce the death of tumor cells and then eliminating the therapeutic stem cells.”
Shah’s team first developed a mouse model that more closely mimics what is seen in patients. They found that injecting into the carotid artery breast cancer cells that express markers allowing them to enter the brain – cells labelled with bioluminescent and fluorescent markers to enable tracking by imaging technologies – resulted in the formation of many metastatic tumours throughout the brain, mimicking what is seen in advanced breast cancer patients. Current therapeutic options for such patients are limited, particularly when there are many metastases.
The scientists then engineered a population of neural stem cells to express a potent version of a gene called TRAIL, which codes for a molecule that activates cell-death-inducing receptors found only on the surface of cancer cells.
Previous research by Shah and his colleagues had shown that two types of stem cells are naturally attracted toward tumours in the brain.
Injecting the TRAIL-expressing stem cells into the carotid artery, a likely strategy for clinical application, led to significantly slower tumor growth and increased survival, compared with animals receiving unaltered stem cells or control injections.
Shah and his team are currently developing similar animal models of brain metastasis from lung cancers and from melanoma.
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