BRAF inhibitors-induced paradoxical reactions and oncogenesis

Abstract

Paradoxical oncogenesis and benign paradoxical proliferations occur in off-target rapidly regenerating labile tissues of patients treated for malignancies with small-molecule inhibitors of cell-signaling such as kinase inhibitors. These paradoxical proliferations, particularly well listed in patients treated with selective BRAF inhibitors carrying BRAF-mutated solid malignancies, have had their incidence reduced upon the advent of BRAF/MEK double blockade therapies. Mechanistically, the underlying molecular events involved in paradoxical proliferations in off-target tissues could prove to be as complex as those involved in the adaptive resistance of malignant cells to targeted therapies.