For the first time a too high response rate of 80% to the novel anti-melanoma drug PLX4032 has been demonstrated. In the August 2010 issue of NEJM , treatment of metastatic melanoma with PLX4032 in selected BRAF (V600E) mutation patients resulted in complete or partial tumor regression in the majority of patients. But this drug activity worked for a mean of 7 months only . Two more recent studies in Nature report mechanisms driving resistance aiming at the discovery of new 'druggable' targets.
The expression of COT, a protein encoding by MAP3K8 gene, was associated with de novo and acquired resistance . Reactivation of the B-RAF signaling pathway or stimulation tumour-cell growth mediated by a different protein found to be related to PLX4032 acquired resistance by another group . Here I discuss the future perspectives of potential understanding mechanisms resistance including signaling pathways networks towards a new generation of more active drugs overcoming resistance.
(Citation: Gastric & Breast Cancer 2010
Oct ; 9(4): 170-174)
This article consists of 5 pages and 3 figures