Browsing by author "Marais, Richard Malcolm"
Now showing items 1-7 of 7
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Effect of SMURF2 Targeting on Susceptibility to MEK Inhibitors in Melanoma
Smith, MP; Ferguson, J; Arozarena, I; Hayward, R; Marais, R; et al. (OXFORD UNIV PRESS INC, 2013-01)The mitogen-activated proteinkinase pathway consisting of the kinases RAF, MEK, and ERK is central to cell proliferation and survival and is deregulated in more than 90% of melanomas. MEK inhibitors are currently trialled ... -
Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.
Wan, PTC; Garnett, MJ; Roe, SM; Lee, S; Niculescu-Duvaz, D; et al. (2004-03)Over 30 mutations of the B-RAF gene associated with human cancers have been identified, the majority of which are located within the kinase domain. Here we show that of 22 B-RAF mutants analyzed, 18 have elevated kinase ... -
Metformin Accelerates the Growth of BRAF(V600E)-Driven Melanoma by Upregulating VEGF-A
Martin, MJ; Hayward, R; Viros, A; Marais, R (AMER ASSOC CANCER RESEARCH, 2012-04)The antidiabetic drug metformin has antitumor activity in a variety of cancers because it blocks cell growth by inhibiting TORC1. Here, we show that melanoma cells that are driven by oncogenic BRAF are resistant to the ... -
Significant differences in biological parameters between prodrugs cleavable by carboxypeptidase G2 that generate 3,5-difluoro-phenol and -aniline nitrogen mustards in gene-directed enzyme prodrug therapy systems.
Niculescu-Duvaz, I; Scanlon, I; Niculescu-Duvaz, D; Friedlos, F; Martin, J; et al. (2004-05)Nine new nitrogen mustard compounds derived from 2,6-difluoro-4-hydroxy- (3a-e) and 2,6-difluoro-4-amino- (4a-d) aniline were synthesized as potential prodrugs. They were designed to be activated to their corresponding ... -
The Immune Microenvironment Confers Resistance to MAPK Pathway Inhibitors through Macrophage-Derived TNF alpha
Smith, MP; Sanchez-Laorden, B; O Brien, K; Brunton, H; Ferguson, J; et al. (AMER ASSOC CANCER RESEARCH, 2014-10)Recently, the rationale for combining targeted therapy with immunotherapy has come to light, but our understanding of the immune response during MAPK pathway inhibitor treatment is limited. We discovered that the immune ... -
The intermediate-activity (L597V)BRAF mutant acts as an epistatic modifier of oncogenic RAS by enhancing signaling through the RAF/MEK/ERK pathway
Andreadi, C; Cheung, L-K; Giblett, S; Patel, B; Jin, H; et al. (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2012-09-01)(L597V)BRAF mutations are acquired somatically in human cancer samples and are frequently coincident with RAS mutations. Germline (L597V)BRAF mutations are also found in several autosomal dominant developmental conditions ... -
Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53
(2014-07)Cutaneous melanoma is epidemiologically linked to ultraviolet radiation (UVR), but the molecular mechanisms by which UVR drives melanomagenesis remain unclear(1,2). The most common somatic mutation in melanoma is a V600E ...