KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target

Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non–Small Cell Lung Cancer

(2017) Pasi A. Jänne et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

(2017) Frances A. Shepherd et al.   JOURNAL OF CLINICAL ONCOLOGY

A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients With Advanced Non–Small Cell Lung Cancer

(2017) David R. Gandara et al.   Journal of Thoracic Oncology

Genetic disruption of oncogenic Kras sensitizes lung cancer cells to Fas receptor-mediated apoptosis

(2017) Haiwei Mou et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer

(2017) Adrian Vallejo et al.   Nature Communications

Progress and prospects of early detection in lung cancer

(2017) Sean Blandin Knight et al.   Open Biology

Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer

(2016) C. A. Carter et al.   ANNALS OF ONCOLOGY

Specific KRAS amino acid substitutions and EGFR mutations predict site-specific recurrence and metastasis following non-small-cell lung cancer surgery

(2016) Stéphane Renaud et al.   BRITISH JOURNAL OF CANCER

Cancer statistics, 2016

(2016) Rebecca L. Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3

(2016) Ying Zhou et al.   CANCER RESEARCH

STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment

(2016) S. Koyama et al.   CANCER RESEARCH

Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma

(2016) Zhong-Yi Dong et al.   CLINICAL CANCER RESEARCH

Nonsquamous, Non-Small-Cell Lung Cancer Patients Who Carry a Double Mutation of EGFR, EML4-ALK or KRAS: Frequency, Clinical-Pathological Characteristics, and Response to Therapy

(2016) Paola Ulivi et al.   Clinical Lung Cancer

Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best Supportive Care in Patients With Stage IV Non–Small-Cell Lung Cancer With a Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based Chemotherapy

(2016) Jonathan W. Goldman et al.   Clinical Lung Cancer

Pooled Analysis of the Prognostic and Predictive Value of KRAS Mutation Status and Mutation Subtype in Patients with Non–Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

(2016) Alona Zer et al.   Journal of Thoracic Oncology

Correlation between KRAS mutation status and response to chemotherapy in patients with advanced non-small cell lung cancer☆

(2016) Megan L. Hames et al.   LUNG CANCER

KRAS and TP53 mutations in bronchoscopy samples from former lung cancer patients

(2016) Weimin Gao et al.   MOLECULAR CARCINOGENESIS

KRAS and the Reality of Personalized Medicine in Non-Small Cell Lung Cancer

(2016) Havva O Kilgoz et al.   MOLECULAR MEDICINE

XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer

(2016) Jimi Kim et al.   NATURE

A combinatorial strategy for treating KRAS-mutant lung cancer

(2016) Eusebio Manchado et al.   NATURE

LKB1 loss links serine metabolism to DNA methylation and tumorigenesis

(2016) Filippos Kottakis et al.   NATURE

Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma

(2016) Chiara Ambrogio et al.   NATURE MEDICINE

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

(2016) P. Lito et al.   SCIENCE

Suppression of KRas-mutant cancer through the combined inhibition of KRAS with PLK1 and ROCK

(2016) Jieqiong Wang et al.   Nature Communications

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

The potential utility of re-mining results of somatic mutation testing: KRAS status in lung adenocarcinoma

(2016) Anna Biernacka et al.   Cancer Genetics

A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†

(2015) G. R. Blumenschein et al.   ANNALS OF ONCOLOGY

A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1)

(2015) S. Ramalingam et al.   ANNALS OF ONCOLOGY

Ras activation revisited: role of GEF and GAP systems

(2015) Anne Hennig et al.   BIOLOGICAL CHEMISTRY

Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer

(2015) P A Jänne et al.   BRITISH JOURNAL OF CANCER

Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non-small cell lung cancer patients with KRAS-activated tumors

(2015) Miguel A. Villalona-Calero et al.   CANCER

Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

(2015) A. D. Cox et al.   CLINICAL CANCER RESEARCH

Monotherapy Administration of Sorafenib in Patients With Non–Small Cell Lung Cancer (MISSION) Trial

(2015) Luis Paz-Ares et al.   Journal of Thoracic Oncology

Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma

(2015) M B Schabath et al.   ONCOGENE

Co-occurring Genomic Alterations Define Major Subsets of KRAS-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities

(2015) F. Skoulidis et al.   Cancer Discovery

Clinical outcome of epidermal growth factor receptor-tyrosine kinase inhibitors therapy for patients with overlapping kirsten rat sarcoma 2 viral oncogene homolog and epidermal growth factor receptor gene mutations

(2015) Hong Zhang et al.   Thoracic Cancer

Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

(2014) S Li et al.   BRITISH JOURNAL OF CANCER

Inhibiting Tankyrases Sensitizes KRAS-Mutant Cancer Cells to MEK Inhibitors via FGFR2 Feedback Signaling

(2014) M. Schoumacher et al.   CANCER RESEARCH

Biomarker Analyses from a Placebo-Controlled Phase II Study Evaluating Erlotinib   Onartuzumab in Advanced Non-Small Cell Lung Cancer: MET Expression Levels Are Predictive of Patient Benefit

(2014) H. Koeppen et al.   CLINICAL CANCER RESEARCH

The evolution of the unstable cancer genome

(2014) Rebecca A Burrell et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012

(2014) Jacques Ferlay et al.   INTERNATIONAL JOURNAL OF CANCER

Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs

(2014) Mark G. Kris et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

KRAS-G12C Mutation Is Associated with Poor Outcome in Surgically Resected Lung Adenocarcinoma

(2014) Ernest Nadal et al.   Journal of Thoracic Oncology

KRAS oncogene substitutions in Korean NSCLC patients: Clinical implication and relationship with pAKT and RalGTPases expression

(2014) Eun Young Kim et al.   LUNG CANCER

Targeting RAS–ERK signalling in cancer: promises and challenges

(2014) Ahmed A. Samatar et al.   NATURE REVIEWS DRUG DISCOVERY

In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C

(2014) J. C. Hunter et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap)

(2013) S. Dearden et al.   ANNALS OF ONCOLOGY

Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors

(2013) Kazunori Honda et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with Genotypically Defined Advanced Non-Small Cell Lung Cancer

(2013) M. A. Socinski et al.   CLINICAL CANCER RESEARCH

ALK Rearrangements Are Mutually Exclusive with Mutations in EGFR or KRAS: An Analysis of 1,683 Patients with Non-Small Cell Lung Cancer

(2013) J. F. Gainor et al.   CLINICAL CANCER RESEARCH

A phase 1b study of trametinib, an oral Mitogen-activated protein kinase kinase (MEK) inhibitor, in combination with gemcitabine in advanced solid tumours

(2013) Jeffrey R. Infante et al.   EUROPEAN JOURNAL OF CANCER

Targeting the RAS oncogene

(2013) Asami Takashima et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Pooled Analysis of the Prognostic and Predictive Effects ofKRASMutation Status andKRASMutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

(2013) Frances A. Shepherd et al.   JOURNAL OF CLINICAL ONCOLOGY

Randomized Phase II Trial of Onartuzumab in Combination With Erlotinib in Patients With Advanced Non–Small-Cell Lung Cancer

(2013) David R. Spigel et al.   JOURNAL OF CLINICAL ONCOLOGY

Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial

(2013) Marina Chiara Garassino et al.   LANCET ONCOLOGY

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

(2013) Jonathan M. Ostrem et al.   NATURE

The quest to overcome resistance to EGFR-targeted therapies in cancer

(2013) Curtis R Chong et al.   NATURE MEDICINE

Coordinate Direct Input of Both KRAS and IGF1 Receptor to Activation of PI3 kinase in KRAS -Mutant Lung Cancer

(2013) Miriam Molina-Arcas et al.   Cancer Discovery

RHOA-FAK Is a Required Signaling Axis for the Maintenance of KRAS-Driven Lung Adenocarcinomas

(2013) Georgia Konstantinidou et al.   Cancer Discovery

The dominant role of G12C over other KRAS mutation types in the negative prediction of efficacy of epidermal growth factor receptor tyrosine kinase inhibitors in non–small cell lung cancer

(2013) Ondrej Fiala et al.   Cancer Genetics

Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer

(2012) Robert C. Doebele et al.   CANCER

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

Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in KrasG12D-LSL mice

(2012) Brett H. Simmons et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A Comprehensive Survey of Ras Mutations in Cancer

(2012) I. A. Prior et al.   CANCER RESEARCH

A Phase II Study of Sorafenib in Patients with Platinum-Pretreated, Advanced (Stage IIIb or IV) Non-Small Cell Lung Cancer with a KRAS Mutation

(2012) A.-M. C. Dingemans et al.   CLINICAL CANCER RESEARCH

First-in-Human, Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of RO5126766, a First-in-Class Dual MEK/RAF Inhibitor in Patients with Solid Tumors

(2012) M. Martinez-Garcia et al.   CLINICAL CANCER RESEARCH

Rationale and Design of MARQUEE: A Phase III, Randomized, Double-Blind Study of Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Patients With Locally Advanced or Metastatic, Nonsquamous, Non–Small-Cell Lung Cancer

(2012) Giorgio V. Scagliotti et al.   Clinical Lung Cancer

KRAS Mutations in Lung Cancer

(2012) Niki Karachaliou et al.   Clinical Lung Cancer

KRAS and BRAF Mutation Analysis in Routine Molecular Diagnostics

(2012) Daniëlle A.M. Heideman et al.   JOURNAL OF MOLECULAR DIAGNOSTICS

Effect of KRAS Oncogene Substitutions on Protein Behavior: Implications for Signaling and Clinical Outcome

(2012) Nathan T. Ihle et al.   JNCI-Journal of the National Cancer Institute

Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial

(2012) Luis Paz-Ares et al.   LANCET ONCOLOGY

Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study

(2012) Pasi A Jänne et al.   LANCET ONCOLOGY

Impact of specific mutant KRAS on clinical outcome of EGFR-TKI-treated advanced non-small cell lung cancer patients with an EGFR wild type genotype

(2012) Giulio Metro et al.   LUNG CANCER

Targeting KRAS-Mutant Non-Small Cell Lung Cancer with the Hsp90 Inhibitor Ganetespib

(2012) J. Acquaviva et al.   MOLECULAR CANCER THERAPEUTICS

Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer

(2011) M. C. Garassino et al.   ANNALS OF ONCOLOGY

c-Raf, but Not B-Raf, Is Essential for Development of K-Ras Oncogene-Driven Non-Small Cell Lung Carcinoma

(2011) Rafael B. Blasco et al.   CANCER CELL

Randomized Phase II Study of Erlotinib Plus Tivantinib Versus Erlotinib Plus Placebo in Previously Treated Non–Small-Cell Lung Cancer

(2011) Lecia V. Sequist et al.   JOURNAL OF CLINICAL ONCOLOGY

A Phase II Trial of Salirasib in Patients with Lung Adenocarcinomas with KRAS Mutations

(2011) Gregory J. Riely et al.   Journal of Thoracic Oncology

Phosphoinositide-3-Kinase Catalytic Alpha and KRAS Mutations are Important Predictors of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Advanced Non-small Cell Lung Cancer

(2011) Vienna Ludovini et al.   Journal of Thoracic Oncology

Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study

(2011) Kenneth J O'Byrne et al.   LANCET ONCOLOGY

GDC-0980 Is a Novel Class I PI3K/mTOR Kinase Inhibitor with Robust Activity in Cancer Models Driven by the PI3K Pathway

(2011) J. J. Wallin et al.   MOLECULAR CANCER THERAPEUTICS

The BATTLE Trial: Personalizing Therapy for Lung Cancer

(2011) Edward S. Kim et al.   Cancer Discovery

Five-year lung cancer survival

(2010) Tina Wang et al.   CANCER

Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation

(2010) Kenichi Suda et al.   CANCER AND METASTASIS REVIEWS

A Synthetic Lethal Interaction between K-Ras Oncogenes and Cdk4 Unveils a Therapeutic Strategy for Non-small Cell Lung Carcinoma

(2010) Marta Puyol et al.   CANCER CELL

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

(2010) Sonja J. Heidorn et al.   CELL

Potential Clinical Significance of a Plasma-Based KRAS Mutation Analysis in Patients with Advanced Non-Small Cell Lung Cancer

(2010) S. Wang et al.   CLINICAL CANCER RESEARCH

A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

(2010) E. B. Haura et al.   CLINICAL CANCER RESEARCH

Analysis of Potential Predictive Markers of Cetuximab Benefit in BMS099, a Phase III Study of Cetuximab and First-Line Taxane/Carboplatin in Advanced Non–Small-Cell Lung Cancer

(2010) Shirin Khambata-Ford et al.   JOURNAL OF CLINICAL ONCOLOGY

Somatic Mutations of the Tyrosine Kinase Domain of Epidermal Growth Factor Receptor and Tyrosine Kinase Inhibitor Response to TKIs in Non-small Cell Lung Cancer: An Analytical Database

(2010) Samuel Murray et al.   Journal of Thoracic Oncology

A Phase II, Open-Label, Randomized Study to Assess the Efficacy and Safety of AZD6244 (ARRY-142886) Versus Pemetrexed in Patients with Non-small Cell Lung Cancer Who Have Failed One or Two Prior Chemotherapeutic Regimens

(2010) John D. Hainsworth et al.   Journal of Thoracic Oncology

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

(2010) Poulikos I. Poulikakos et al.   NATURE

Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

(2010) Eunice L. Kwak et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Gene Expression Signature Associated with “K-Ras Addiction” Reveals Regulators of EMT and Tumor Cell Survival

(2009) Anurag Singh et al.   CANCER CELL

Sorafenib Inhibits Non-Small Cell Lung Cancer Cell Growth by Targeting B-RAF in KRAS Wild-Type Cells and C-RAF in KRAS Mutant Cells

(2009) K. Takezawa et al.   CANCER RESEARCH

A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene

(2009) Ji Luo et al.   CELL

KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies

(2009) Chen Mao et al.   LUNG CANCER

Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1

(2009) David A. Barbie et al.   NATURE

Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance

(2008) N. T. Ihle et al.   CANCER RESEARCH

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer

(2008) Giorgio Vittorio Scagliotti et al.   JOURNAL OF CLINICAL ONCOLOGY

Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer

(2008) Helena Linardou et al.   LANCET ONCOLOGY

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