The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches

A phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765 (SAR245409), a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced malignancies.

(2017) I. Brana et al.   JOURNAL OF CLINICAL ONCOLOGY

PLX4032 in metastatic colorectal cancer patients with mutant BRAF tumors.

(2017) S. Kopetz et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-human, safety, pharmacodynamic (PD) and pharmacokinetic (PK) trial of a first-in-class dual RAF/MEK inhibitor, RO5126766, in patients with advanced or metastatic solid tumors.

(2017) S. O. Dolly et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase I dose-escalation study of oral MK-2206 (allosteric AKT inhibitor) with oral selumetinib (AZD6244; MEK inhibitor) in patients with advanced or metastatic solid tumors.

(2017) A. W. Tolcher et al.   JOURNAL OF CLINICAL ONCOLOGY

A dose-escalation study with the novel formulation of the oral pan-class I PI3K inhibitor BEZ235, solid dispersion system (SDS) sachet, in patients with advanced solid tumors.

(2017) J. D. Peyton et al.   JOURNAL OF CLINICAL ONCOLOGY

AKT Inhibition Relieves Feedback Suppression of Receptor Tyrosine Kinase Expression and Activity

(2011) Sarat Chandarlapaty et al.   CANCER CELL

MEK1 mutations, but not ERK2 mutations, occur in melanomas and colon carcinomas, but none in thyroid carcinomas

(2011) Avaniyapuram Kannan Murugan et al.   CELL CYCLE

Activity of XL184 (Cabozantinib), an Oral Tyrosine Kinase Inhibitor, in Patients With Medullary Thyroid Cancer

(2011) Razelle Kurzrock et al.   JOURNAL OF CLINICAL ONCOLOGY

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

(2011) Paul B. Chapman et al.   NEW ENGLAND JOURNAL OF MEDICINE

PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer

(2011) V Serra et al.   ONCOGENE

Non-genomic loss of PTEN function in cancer: not in my genes

(2011) Nick R. Leslie et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy

(2010) K H T Paraiso et al.   BRITISH JOURNAL OF CANCER

4E-BP1 Is a Key Effector of the Oncogenic Activation of the AKT and ERK Signaling Pathways that Integrates Their Function in Tumors

(2010) Qing-Bai She et al.   CANCER CELL

PIK3CA Mutation Uncouples Tumor Growth and Cyclin D1 Regulation from MEK/ERK and Mutant KRAS Signaling

(2010) E. Halilovic et al.   CANCER RESEARCH

Cell Signaling by Receptor Tyrosine Kinases

(2010) Mark A. Lemmon et al.   CELL

Targeting the Mitogen-Activated Protein Kinase Pathway: Physiological Feedback and Drug Response

(2010) C. A. Pratilas et al.   CLINICAL CANCER RESEARCH

ERK1/2 Phosphorylate Raptor to Promote Ras-dependent Activation of mTOR Complex 1 (mTORC1)

(2010) Audrey Carriere et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Clinical Implications of the Cancer Genome

(2010) Laura E. MacConaill et al.   JOURNAL OF CLINICAL ONCOLOGY

The PI3K Pathway As Drug Target in Human Cancer

(2010) Kevin D. Courtney et al.   JOURNAL OF CLINICAL ONCOLOGY

The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas

(2009) K Shoji et al.   BRITISH JOURNAL OF CANCER

Function, regulation and pathological roles of the Gab/DOS docking proteins

(2009) Franziska U Wöhrle et al.   Cell Communication and Signaling

Molecular alterations inAKT1,AKT2andAKT3detected in breast and prostatic cancer by FISH

(2009) Tove Kirkegaard et al.   HISTOPATHOLOGY

FrequentPIK3CAgene amplification and its clinical significance in colorectal cancer

(2009) Zeenath Jehan et al.   JOURNAL OF PATHOLOGY

mTORC1-Activated S6K1 Phosphorylates Rictor on Threonine 1135 and Regulates mTORC2 Signaling

(2009) L.-A. Julien et al.   MOLECULAR AND CELLULAR BIOLOGY

Implications for KRAS status and EGFR-targeted therapies in metastatic CRC

(2009) Nicola Normanno et al.   Nature Reviews Clinical Oncology

Targeting the phosphoinositide 3-kinase pathway in cancer

(2009) Pixu Liu et al.   NATURE REVIEWS DRUG DISCOVERY

A novel AKT3 mutation in melanoma tumours and cell lines

(2008) M A Davies et al.   BRITISH JOURNAL OF CANCER

Oncogenic MAPK Signaling Stimulates mTORC1 Activity by Promoting RSK-Mediated Raptor Phosphorylation

(2008) Audrey Carrière et al.   CURRENT BIOLOGY

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

(2008) Roger McLendon et al.   NATURE

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers

(2008) Jeffrey A Engelman et al.   NATURE MEDICINE

The role of PTEN signaling perturbations in cancer and in targeted therapy

(2008) M Keniry et al.   ONCOGENE

PI3K pathway alterations in cancer: variations on a theme

(2008) T L Yuan et al.   ONCOGENE

Helical domain and kinase domain mutations in p110  of phosphatidylinositol 3-kinase induce gain of function by different mechanisms

(2008) L. Zhao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA