MEK and PI3K inhibition in solid tumors: rationale and evidence to date

A phase I study evaluating GDC-0941, an oral phosphoinositide-3 kinase (PI3K) inhibitor, in patients with advanced solid tumors or multiple myeloma.

(2017) V. Moreno Garcia et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I Expansion and Pharmacodynamic Study of the Oral MEK Inhibitor RO4987655 (CH4987655) in Selected Patients with Advanced Cancer with RAS-RAF Mutations

(2014) L. Zimmer et al.   CLINICAL CANCER RESEARCH

Comprehensive molecular characterization of gastric adenocarcinoma

(2014) Adam J. Bass et al.   NATURE

Comprehensive molecular profiling of lung adenocarcinoma

(2014) Eric A. Collisson et al.   NATURE

Comprehensive molecular characterization of urothelial bladder carcinoma

(2014)   NATURE

Multicenter Phase I Trial of the Mitogen-Activated Protein Kinase 1/2 Inhibitor BAY 86-9766 in Patients with Advanced Cancer

(2013) C. D. Weekes et al.   CLINICAL CANCER RESEARCH

Evaluation and Clinical Analyses of Downstream Targets of the Akt Inhibitor GDC-0068

(2013) Y. Yan et al.   CLINICAL CANCER RESEARCH

Integrated genomic characterization of endometrial carcinoma

(2013) Gad Getz et al.   NATURE

Molecular targets on the horizon for kidney and urothelial cancer

(2013) Joaquim Bellmunt et al.   Nature Reviews Clinical Oncology

Selumetinib-Enhanced Radioiodine Uptake in Advanced Thyroid Cancer

(2013) Alan L. Ho et al.   NEW ENGLAND JOURNAL OF MEDICINE

mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1

(2013) A. C. Faber et al.   Cancer Discovery

Alternative dosing of dual PI3K and MEK inhibition in cancer therapy

(2012) Elina Jokinen et al.   BMC CANCER

Clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment

(2012) Irene Brana et al.   BMC Medicine

Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS Mutant Cancer Models

(2012) Ryan B. Corcoran et al.   CANCER CELL

MEK Inhibition Leads to PI3K/AKT Activation by Relieving a Negative Feedback on ERBB Receptors

(2012) A. B. Turke et al.   CANCER RESEARCH

Phase I Study of the Combination of Sorafenib and Temsirolimus in Patients with Metastatic Melanoma

(2012) M. A. Davies et al.   CLINICAL CANCER RESEARCH

Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial

(2012) Axel Hauschild et al.   LANCET

Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial

(2012) Jeffrey R Infante et al.   LANCET ONCOLOGY

Comprehensive molecular characterization of human colon and rectal cancer

(2012)   NATURE

Comprehensive molecular portraits of human breast tumours

(2012) Daniel C. Koboldt et al.   NATURE

Comprehensive genomic characterization of squamous cell lung cancers

(2012)   NATURE

Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

(2012) Margaret K. Callahan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations

(2012) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

RASMutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors

(2012) Fei Su et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

(2011) Sarat Chandarlapaty et al.   CANCER CELL

Intermittent Administration of MEK Inhibitor GDC-0973 plus PI3K Inhibitor GDC-0941 Triggers Robust Apoptosis and Tumor Growth Inhibition

(2011) K. P. Hoeflich et al.   CANCER RESEARCH

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy

(2011) Seth A. Wander et al.   JOURNAL OF CLINICAL INVESTIGATION

Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors

(2011) Johanna C. Bendell et al.   JOURNAL OF CLINICAL ONCOLOGY

Integrated genomic analyses of ovarian carcinoma

(2011) D. Bell et al.   NATURE

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

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

Everolimus for Advanced Pancreatic Neuroendocrine Tumors

(2011) James C. Yao et al.   NEW ENGLAND JOURNAL OF MEDICINE

Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

(2011) José Baselga et al.   NEW ENGLAND JOURNAL OF MEDICINE

PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs

(2011) B Weigelt et al.   ONCOGENE

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

(2011) V Serra et al.   ONCOGENE

Recent Developments in Anti-Cancer Agents Targeting PI3K, Akt and mTORC1/2

(2011) Rodrigo Dienstmann et al.   Recent Patents on Anti-Cancer Drug Discovery

The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

(2011) Michelle C. Mendoza et al.   TRENDS IN BIOCHEMICAL SCIENCES

PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer

(2010) Tarek A. Bismar et al.   BJU INTERNATIONAL

A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens

(2010) Jaafar Bennouna et al.   INVESTIGATIONAL NEW DRUGS

RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

(2010) Poulikos I. Poulikakos et al.   NATURE

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma

(2010) Gideon Bollag et al.   NATURE

Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy

(2010) Jordi Barretina et al.   NATURE GENETICS

AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer

(2009) Krishna M. Vasudevan et al.   CANCER CELL

In vivo Antitumor Activity of MEK and Phosphatidylinositol 3-Kinase Inhibitors in Basal-Like Breast Cancer Models

(2009) K. P. Hoeflich et al.   CLINICAL CANCER RESEARCH

Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer

(2009) M. L. Sos et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells

(2009) Saskia M. Brachmann et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition

(2009) A. C. Faber et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Farnesyltransferase Inhibitors: A Detailed Chemical View on an Elusive Biological Problem

(2008) Sergio Sousa et al.   CURRENT MEDICINAL CHEMISTRY

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 (ARRY-142886) in Patients With Advanced Cancers

(2008) Alex A. Adjei et al.   JOURNAL OF CLINICAL ONCOLOGY

Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial

(2008) Robert J Motzer et al.   LANCET

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

(2008) Scott M. Wilhelm et al.   MOLECULAR CANCER THERAPEUTICS

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

Sorafenib in Advanced Hepatocellular Carcinoma

(2008) Josep M. Llovet et al.   NEW ENGLAND JOURNAL OF MEDICINE