Advances in the Development of Cancer Therapeutics Directed against the RAS-Mitogen-Activated Protein Kinase Pathway

The Hallmarks of Cancer

2000 • 27,569 citations

Mutations of the BRAF gene in human cancer

2002 • 10,249 citations

A synthetic inhibitor of the mitogen-activated protein kinase cascade.

1995 • 2,723 citations

Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer

2007 • 2,651 citations

Discovery and development of sorafenib: a multikinase inhibitor for treating cancer

2006 • 1,693 citations

BRAF mutation predicts sensitivity to MEK inhibition

2005 • 1,312 citations

Melanoma biology and new targeted therapy

2007 • 1,306 citations

The RAF proteins take centre stage

2004 • 1,158 citations

Targeting the mitogen-activated protein kinase cascade to treat cancer

2004 • 1,093 citations

Coordinating ERK/MAPK signalling through scaffolds and inhibitors

2005 • 1,039 citations

Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo

1999 • 970 citations

Defective Thymocyte Maturation in p44 MAP Kinase (Erk 1) Knockout Mice

1999 • 641 citations

Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer

2004 • 631 citations

Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition

2004 • 588 citations

Biological Characterization of ARRY-142886 (AZD6244), a Potent, Highly Selective Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor

2007 • 556 citations

HSP90 as a new therapeutic target for cancer therapy: the story unfolds

2002 • 526 citations

Differential Regulation of Raf-1, A-Raf, and B-Raf by Oncogenic Ras and Tyrosine Kinases

1997 • 446 citations

Phase I and Pharmacodynamic Study of the Oral MEK Inhibitor CI-1040 in Patients With Advanced Malignancies

2005 • 400 citations

AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models

2007 • 379 citations

Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells.

1992 • 370 citations

Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta

1999 • 337 citations

Raf: A Strategic Target for Therapeutic Development Against Cancer

2005 • 292 citations

Isotype-Specific Functions of Raf Kinases

1999 • 259 citations

Demonstration of a Genetic Therapeutic Index for Tumors Expressing Oncogenic BRAF by the Kinase Inhibitor SB-590885

2006 • 251 citations

A functional RNAi screen for regulators of receptor tyrosine kinase and ERK signalling

2006 • 210 citations

Mutations of C-RAF Are Rare in Human Cancer because C-RAF Has a Low Basal Kinase Activity Compared with B-RAF

2005 • 199 citations

A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells

2005 • 177 citations

Clinical experience of MEK inhibitors in cancer therapy

2006 • 173 citations

Mek2 Is Dispensable for Mouse Growth and Development

2003 • 172 citations

Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf

2004 • 160 citations

Ordered phosphorylation of p42^mapk by MAP kinase kinase

1992 • 159 citations

The role of B-RAF in melanoma

2005 • 156 citations

Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf

2004 • 155 citations

Absence of the CAAX Endoprotease Rce1: Effects on Cell Growth and Transformation

2002 • 146 citations

RAS and RAF-1 form a signalling complex with MEK-1 but not MEK-2.

1994 • 121 citations

Tumor Necrosis Factor-α Blocks Apoptosis in Melanoma Cells when BRAF Signaling Is Inhibited

2007 • 119 citations

MEK Inhibitors: A Therapeutic Approach to Targeting the Ras-MAP Kinase Pathway in Tumors

2004 • 112 citations

Ki67 expression levels are a better marker of reduced melanoma growth following MEK inhibitor treatment than phospho-ERK levels

2007 • 106 citations

A phase 1–2 clinical study of a second generation oral MEK inhibitor, PD 0325901 in patients with advanced cancer

2005 • 91 citations

Identification of signalling proteins interacting with B-Raf in the yeast two-hybrid system.

1996 • 77 citations

Recent Advances of MEK Inhibitors and Their Clinical Progress

2007 • 73 citations

3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography Is a Sensitive Method for Imaging the Response of BRAF-Dependent Tumors to MEK Inhibition

2007 • 66 citations

Pharmacologic Inhibitors of MKK1 and MKK2

2001 • 64 citations

Raf pathway inhibitors in oncology.

2003 • 59 citations

The Isoprenoid Substrate Specificity of Isoprenylcysteine Carboxylmethyltransferase

2005 • 38 citations

High-throughput approaches to dissecting MAPK signaling pathways

2006 • 33 citations

Pharmacokinetics (PK) and pharmacodynamics (PD) of PD 0325901, a second generation MEK inhibitor after multiple oral doses of PD 0325901 to advanced cancer patients

2005 • 28 citations

Preclinical development of ARRY-142886, a potent and selective MEK inhibitor

2004 • 17 citations

Clinical aspects of a phase I study of PD-0325901, a selective oral MEK inhibitor, in patients with advanced cancer

2007 • 16 citations

XL518, a potent selective orally bioavailable MEK1 inhibitor, downregulates the RAS/RAF/MEK/ERK pathway in vivo, resulting in tumor growth inhibition and regression in pre-clinical models

2007 • 13 citations

Pharmacokinetic (PK) and pharmacodynamic (PD) results of a phase I study of PD-0325901, a second generation oral MEK inhibitor, in patients with advanced cancer

2007 • 8 citations

26 ORAL Phase Ib and pharmacodynamic study of the MEK inhibitor AZD6244 (ARRY-142886) in patients with advanced solid malignancies

2006 • 7 citations

Plx4032, a selective b-rafV600E inhibitor has potent anti-tumor activity in b-rafV600E-bearing colorectal xenografts and shows additive effect with other chemoagents

2007 • 4 citations

RDEA119: A potent and highly selective MEK inhibitor for the treatment of cancer

2007 • 3 citations