Do the Side Effects of BRAF Inhibitors Mimic RASopathies?

Abstract

Recent advances in targeted anticancer therapies have substantially improved the prognosis of several cancers. Such targeted therapies are not, however, free of side effects, and these side effects are clearly distinct from those induced by classical cytotoxic chemotherapies. This is likely so because targeted therapies are designed to interfere with specific oncogenic signaling pathways rather than to inhibit cell proliferation in general. In fact, interference with specific signaling pathways may lead to effects that mimic those associated with genetic disorders due to alterations in the corresponding signaling pathways. Here, we compare the clinical effects of treatment with BRAF inhibitors with those of genetic RASopathies and find a striking overlap between the inhibitor-induced, iatrogenic dermatoses with the genodermatoses seen in patients with corresponding congenital RASopathies. We hope that such comparisons lead to a better understanding of the side effects of targeted therapies.