Current best practices and rationalistic perspectives in causation-based prevention, early detection and multidisciplinary treatment of breast and gastric cancer

Gastric & Breast Cancer e-journal
DOI: 10.2122/gbc.2012.0251


Trametinib plus dabrafenib : Targeting RAS-MAPK pathway for BRAF V600-mutant melanoma.

Chee-Seng Ku, MD, PhD.

Affiliation: Chee-Seng Ku, Cancer Science Institute of Singapore, National University of Singapore, Singapore.


Genetic and epigenetic changes and signalling pathways activation drive carcinogenesis, tumor growth and metastasis. One of several signalling pathways involved in ~ 20% of cancers is the RAF-MEK-ERK pathway that is activated through RAS oncoproteins or mutations in these genes [1]. In 66% of melanomas and in lower frequency for other cancer types, activating mutations in BRAF have been found. Despite progression-free survival and overall survival benefit with vemurafenib and dabrafenib that are BRAF and MEK inhibitors of BRAFV600-mutant advanced melanomas respectively [2,3], resistance occurs in more than 50% of patients. In a more recent phase 1 and 2 study, the BRAF-MEK complex of dabrafenib plus trametinib inhibitors has been evaluated for metastatic melanoma patients with BRAF V600 mutations [4]. Can this combined treatment decrease resistance for improving survival of these patients?

(Citation: Gastric & Breast Cancer 2012; 11(4): 208-210)

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last update: 31 October 2012