[HTML][HTML] Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy
The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-
ERK signal cascade, functions to transmit upstream signals to its downstream effectors to …
ERK signal cascade, functions to transmit upstream signals to its downstream effectors to …
Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring
D Ménard, I Niculescu-Duvaz, HP Dijkstra… - Journal of medicinal …, 2009 - ACS Publications
BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts
as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have …
as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have …
Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors.
R Kefford, H Arkenau, MP Brown, M Millward… - Journal of Clinical …, 2010 - ascopubs.org
8503 Background: GSK2118436 is a highly potent and selective ATP competitive BRAF
inhibitor with> 100-fold selectivity for mutant (mut) BRAF over wild type (wt) in cell lines. It …
inhibitor with> 100-fold selectivity for mutant (mut) BRAF over wild type (wt) in cell lines. It …
The complexity of the ERK/MAP-kinase pathway and the treatment of melanoma skin cancer
C Wellbrock, I Arozarena - Frontiers in cell and developmental biology, 2016 - frontiersin.org
The central role played by the ERK/MAPK pathway downstream of RAS in human
neoplasias is best exemplified in the context of melanoma skin cancer. Signaling through …
neoplasias is best exemplified in the context of melanoma skin cancer. Signaling through …
Emerging RAF inhibitors
JA McCubrey, LS Steelman, SL Abrams… - Expert opinion on …, 2009 - Taylor & Francis
Background: The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often
activated by genetic alterations in upstream signaling molecules. An integral component of …
activated by genetic alterations in upstream signaling molecules. An integral component of …
Dividing and conquering: controlling advanced melanoma by targeting oncogene-defined subsets
KT Flaherty - Clinical & experimental metastasis, 2012 - Springer
For decades, therapy for advanced melanoma has lagged behind most of the cancer field
owing to its intrinsic resistance to conventional cytotoxic chemotherapy and limited impact of …
owing to its intrinsic resistance to conventional cytotoxic chemotherapy and limited impact of …
BRAF and MEK inhibition for the treatment of advanced BRAF mutant melanoma
J Richman, J Martin-Liberal, S Diem… - Expert opinion on …, 2015 - Taylor & Francis
Introduction: BRAF inhibition alone has achieved unprecedented efficacy results in patients
affected by BRAF-mutated advanced melanoma. Since these findings, it was postulated that …
affected by BRAF-mutated advanced melanoma. Since these findings, it was postulated that …
Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions
AJ King, MR Arnone, MR Bleam, KG Moss, J Yang… - PloS one, 2013 - journals.plos.org
Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many
types of human cancer. BRAF mutations that constitutively activate MAPK signalling and …
types of human cancer. BRAF mutations that constitutively activate MAPK signalling and …
Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K
J Villanueva, A Vultur, JT Lee, R Somasundaram… - Cancer cell, 2010 - cell.com
BRAF is an attractive target for melanoma drug development. However, resistance to BRAF
inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF …
inhibitors is a significant clinical challenge. We describe a model of resistance to BRAF …
Dual inhibition of MAPK and JAK2/STAT3 pathways is critical for the treatment of BRAF mutant melanoma
K Zhao, Y Lu, Y Chen, J Cheng, W Zhang - Molecular Therapy-Oncolytics, 2020 - cell.com
BRAF and MEK inhibitors significantly prolong progression-free survival in patients with
BRAF mutant melanoma. However, most patients quickly develop drug resistance. The …
BRAF mutant melanoma. However, most patients quickly develop drug resistance. The …