Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response

CA Pratilas, DB Solit - Clinical Cancer Research, 2010 - AACR
Mitogen-activated protein kinase (MAPK) pathway activation is a frequent event in human
cancer and is often the result of activating mutations in the BRAF and RAS oncogenes …

[HTML][HTML] BRAF mutations and the utility of RAF and MEK inhibitors in primary brain tumors

KC Schreck, SA Grossman, CA Pratilas - Cancers, 2019 - mdpi.com
BRAF mutations have been identified as targetable, oncogenic mutations in many cancers.
Given the paucity of treatments for primary brain tumors and the poor prognosis associated …

BRAF mutation predicts sensitivity to MEK inhibition

DB Solit, LA Garraway, CA Pratilas, A Sawai, G Getz… - Nature, 2006 - nature.com
The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK)
and extracellular signal regulated kinase (ERK) is activated in most human tumours, often …

V600EBRAF is associated with disabled feedback inhibition of RAF–MEK signaling and elevated transcriptional output of the pathway

CA Pratilas, BS Taylor, Q Ye, A Viale… - Proceedings of the …, 2009 - National Acad Sciences
Tumors with mutant BRAF and those with receptor tyrosine kinase (RTK) activation have
similar levels of phosphorylated ERK, but only the former depend on ERK signaling for …

[PDF][PDF] Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas

P Lito, CA Pratilas, EW Joseph, M Tadi, E Halilovic… - Cancer cell, 2012 - cell.com
Summary BRAF V600E drives tumors by dysregulating ERK signaling. In these tumors, we
show that high levels of ERK-dependent negative feedback potently suppress ligand …

The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner

EW Joseph, CA Pratilas… - Proceedings of the …, 2010 - National Acad Sciences
Tumors with mutant BRAF and some with mutant RAS are dependent upon ERK signaling
for proliferation, and their growth is suppressed by MAPK/ERK kinase (MEK) inhibitors. In …

Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence

MH Nissan, CA Pratilas, AM Jones, R Ramirez, H Won… - Cancer research, 2014 - AACR
Melanoma is a disease characterized by lesions that activate ERK. Although 70% of
cutaneous melanomas harbor activating mutations in the BRAF and NRAS genes, the …

Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors

D Ercan, C Xu, M Yanagita, CS Monast, CA Pratilas… - Cancer discovery, 2012 - AACR
The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors is limited
by the development of drug resistance. The irreversible EGFR kinase inhibitor WZ4002 is …

Genomic and biological characterization of exon 4 KRAS mutations in human cancer

M Janakiraman, E Vakiani, Z Zeng, CA Pratilas… - Cancer research, 2010 - AACR
Mutations in RAS proteins occur widely in human cancer. Prompted by the confirmation of
KRAS mutation as a predictive biomarker of response to epidermal growth factor receptor …

Transcriptional pathway signatures predict MEK addiction and response to selumetinib (AZD6244)

JR Dry, S Pavey, CA Pratilas, C Harbron, S Runswick… - Cancer research, 2010 - AACR
Abstract Selumetinib (AZD6244, ARRY-142886) is a selective, non–ATP-competitive
inhibitor of mitogen-activated protein/extracellular signal–regulated kinase kinase (MEK) …