Targeted therapies anonymous.

Drug addiction runs deeper than we thought. It goes something like this: you start dabrafenib and trametinib for melanoma and get a good response, only to have resistant clones emerge 3-5 months later. Interestingly, these clones die en masse if the drugs are discontinued because they are not only tolerant to therapy but are actually dependent on its presence for survival. Of course, there are always a small subset of cells that are able to survive withdrawal. A novel study in Nature now reports this “drug addiction pathway” is dependent on the signaling of ERK2 kinase. So cells without ERK2 survive withdrawal. What’s worse, drug-addicted ERK2-deficient cells can undergo a phenotypic switch from simply proliferative to full-blown metastatic during withdrawal...so the cells that do survive withdrawal are pretty nasty. The bright side? There may be a narrow therapeutic window we can harness to eradicate these cells surviving withdrawal by switching to a different therapy altogether. And this pub may grant us the wisdom to know that difference.