Do the Side Effects of BRAF Inhibitors Mimic RASopathies?
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.
Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France.
Alicia
A
Sfecci
Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France; Division of Medicine, Université de Rennes 1, Rennes, France; CNRS UMR6290, GEO team, IGDR, Rennes, France.
Alain
A
Dupuy
Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France.
Monica
M
Dinulescu
Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France; Division of Medicine, Université de Rennes 1, Rennes, France.
Catherine
C
Droitcourt
Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France.
Henri
H
Adamski
Department of Dermatology, Centre National de Référence des Maladies Génétiques à Expression Cutanée (MAGEC), Hôpital Universitaire Necker-Enfants Malades, APHP, Institut Imagine, Paris, France; Unité INSERM U1163, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France.
Smail
S
Hadj-Rabia
Division of Medicine, Université de Rennes 1, Rennes, France; Department of Clinical Genetics, Centre de Référence des Anomalies du Développement CLAD-Ouest, CNRS UMR 6290, Sud Hospital, CHU de Rennes, Rennes, France.
Sylvie
S
Odent
Division of Medicine, Université de Rennes 1, Rennes, France; CNRS UMR6290, GEO team, IGDR, Rennes, France; Department of Somatic Cancer Genetics, Pontchaillou Hospital, CHU de Rennes, Rennes, France.
Marie-Dominique
MD
Galibert
Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, France; Division of Medicine, Université de Rennes 1, Rennes, France; CNRS UMR6290, GEO team, IGDR, Rennes, France. Electronic address: lise.boussemart@chu-rennes.fr.
Lise
L
Boussemart
D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000009:adverse effects* / Q000379:methods; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000187:drug effects* / Q000235:genetics; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf