Figures & data
(A) In cells expressing mutant BRAF, overexpression of RAF1 or activation of RAS due to N-RAS mutation results in the formation of BRAF–RAF1 heterodimers and/or RAF1–RAF1 homodimers, causing resistance to PLX4032. Alternatively, overexpression of COT results in RAF-independent activation of MEK and ERK, and thus resistance to PLX4032. In such cells, therefore, PLX4032 resistance is mediated by reactivation of the MAPK–ERK signaling pathway. (B) Another possibility is that activation of upstream RTKs such as PDGFRβ makes MEK activity redundant by triggering downstream effectors of cell transformation through parallel signaling pathways.
PDGFRβ: PDGF receptor-β
Reproduced from Citation[4,5], with permission from Nature Publishing Group.
![Figure 1. The short and long roads to PLX4032 resistance.(A) In cells expressing mutant BRAF, overexpression of RAF1 or activation of RAS due to N-RAS mutation results in the formation of BRAF–RAF1 heterodimers and/or RAF1–RAF1 homodimers, causing resistance to PLX4032. Alternatively, overexpression of COT results in RAF-independent activation of MEK and ERK, and thus resistance to PLX4032. In such cells, therefore, PLX4032 resistance is mediated by reactivation of the MAPK–ERK signaling pathway. (B) Another possibility is that activation of upstream RTKs such as PDGFRβ makes MEK activity redundant by triggering downstream effectors of cell transformation through parallel signaling pathways.PDGFRβ: PDGF receptor-βReproduced from Citation[4,5], with permission from Nature Publishing Group.](/cms/asset/caf2ae04-7dd9-419e-bcac-79cda99400dc/iery_a_11219683_f0001_b.jpg)
