Around half of melanomas are caused by a mutation in a gene called BRAF. Drugs called BRAF inhibitors treat these melanomas by targeting the faulty gene. But these cancers can quickly develop resistance to these targeted treatments.
Scientists at the Francis Crick Institute, (link is external) funded by Cancer Research UK, and at the Cancer Research UK Manchester Institute (link is external) have discovered that a side effect of BRAF inhibitors is that they prompt healthy cells to form a ‘safe haven’ shielding melanoma cells from cancer drugs. So even if some cancer cells are destroyed, the protected cancer cells may survive – and the disease can recur in a form that is untreatable.
Carried out in cells in the laboratory, in mice and in samples from patients’ tumours, the researchers showed this ‘safe haven’ lets melanoma cells turn on a parallel set of cell signals that helps them survive. By adding a second experimental drug that blocks this alternative survival route by targeting a protein called FAK, the researchers discovered that resistance to BRAF inhibitors can be overcome. This combination of two drugs increased cell death and slowed growth in cell samples, and also stopped tumours from growing larger in mice.
Link to research: Hirata et al., Intravital Imaging Reveals How BRAF Inhibition Generates Drug-Tolerant Microenvironments with High Integrin b1/FAK Signaling, Cancer Cell (2015)
Picture credit: Dr Erik Sahai