Parallel and Serial Blockade Strategies in BRAF-Mutant Melanoma

摘要: Activating mutations in BRAF are the most common somatic aberration cutaneous melanomas. These result constitutive activation of BRAF’s catalytic activity and its downstream effectors RAS-RAF-MEK-ERK signaling pathway. Both selective MEK inhibitors have demonstrated high clinical response rates metastatic melanoma patients with activating mutations. successes illustrated several keys to successful development targeted therapies, potential for personalized therapeutic strategies cancer. However, ultimate benefit has been limited by both de novo secondary resistance mechanisms. Initial preclinical studies support that these mechanisms may broadly be characterized as those (1) re-activation pathway, or (2) other pro-survival mediators. findings now leading new combinatorial approaches involve serial and/or parallel blockade order overcome mechanisms, ultimately improve outcomes Further, concepts also being explored tested oncogenic