Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

(2018) Matthew R. Janes et al.   CELL

Assessing Therapeutic Efficacy of MEK Inhibition in a KRAS G12C-Driven Mouse Model of Lung Cancer

(2018) Shuai Li et al.   CLINICAL CANCER RESEARCH

phospho-ERK is a biomarker of response to a synthetic lethal drug combination of sorafenib and MEK inhibition in liver cancer

(2018) Cun Wang et al.   JOURNAL OF HEPATOLOGY

SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo

(2018) Sara Mainardi et al.   NATURE MEDICINE

Targeting the PI3K pathway in cancer: are we making headway?

(2018) Filip Janku et al.   Nature Reviews Clinical Oncology

Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF V600E -Mutant Colorectal Cancer

(2018) Ryan B. Corcoran et al.   Cancer Discovery

Differential Effector Engagement by Oncogenic KRAS

(2018) Tina L. Yuan et al.   Cell Reports

KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition

(2018) Sandra Misale et al.   CLINICAL CANCER RESEARCH

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

An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer

(2017) Yaohua Xue et al.   NATURE MEDICINE

Dosing Three‐Drug Combinations That Include Targeted Anti‐Cancer Agents: Analysis of 37,763 Patients

(2017) Mina Nikanjam et al.   ONCOLOGIST

Direct inhibition of RAS: Quest for the Holy Grail?

(2017) Russell Spencer-Smith et al.   SEMINARS IN CANCER BIOLOGY

A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

(2017) Grace R. Anderson et al.   Cell Reports

Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors

(2017) Mark Merchant et al.   PLoS One

A phase Ib dose-escalation study of the MEK inhibitor trametinib in combination with the PI3K/mTOR inhibitor GSK2126458 in patients with advanced solid tumors

(2016) J. E. Grilley-Olson et al.   INVESTIGATIONAL NEW DRUGS

A combinatorial strategy for treating KRAS-mutant lung cancer

(2016) Eusebio Manchado et al.   NATURE

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

(2016) P. Lito et al.   SCIENCE

Epithelial-to-Mesenchymal Transition Defines Feedback Activation of Receptor Tyrosine Kinase Signaling Induced by MEK Inhibition in KRAS-Mutant Lung Cancer

(2016) H. Kitai et al.   Cancer Discovery

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

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

Rational Selection of Syngeneic Preclinical Tumor Models for Immunotherapeutic Drug Discovery

(2016) Suzanne I.S. Mosely et al.   Cancer Immunology Research

Current treatment strategies for inhibiting mTOR in cancer

(2015) Francesca Chiarini et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

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

Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach

(2015) Alexandra Pender et al.   PLoS One

A phase IB trial of the oral MEK inhibitor trametinib (GSK1120212) in combination with everolimus in patients with advanced solid tumors

(2014) A. W. Tolcher et al.   ANNALS OF ONCOLOGY

A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer

(2014) Johanna C. Bendell et al.   INVESTIGATIONAL NEW DRUGS

Comprehensive molecular profiling of lung adenocarcinoma

(2014) Eric A. Collisson et al.   NATURE

The mutational landscapes of genetic and chemical models of Kras-driven lung cancer

(2014) Peter M. K. Westcott et al.   NATURE

Intrinsic Resistance to MEK Inhibition in KRAS Mutant Lung and Colon Cancer through Transcriptional Induction of ERBB3

(2014) Chong Sun et al.   Cell Reports

RAF Suppression Synergizes with MEK Inhibition in KRAS Mutant Cancer Cells

(2014) Simona Lamba et al.   Cell Reports

Everolimus: side effect profile and management of toxicities in breast cancer

(2013) Elisavet Paplomata et al.   BREAST CANCER RESEARCH AND TREATMENT

Requirement for Interaction of PI3-Kinase p110α with RAS in Lung Tumor Maintenance

(2013) Esther Castellano et al.   CANCER CELL

PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types

(2013) Carolyn D. Britten   CANCER CHEMOTHERAPY AND PHARMACOLOGY

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

(2013) Jonathan M. Ostrem et al.   NATURE

TORC1 Suppression Predicts Responsiveness to RAF and MEK Inhibition in BRAF-Mutant Melanoma

(2013) R. B. Corcoran et al.   Science Translational Medicine

mTORC1 Inhibition Is Required for Sensitivity to PI3K p110  Inhibitors in PIK3CA-Mutant Breast Cancer

(2013) M. Elkabets et al.   Science Translational 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

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

A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response

(2012) Zhao Chen et al.   NATURE

Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils

(2011) Davide Torti et al.   EMBO Molecular Medicine

Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers

(2011) Hiromichi Ebi et al.   JOURNAL OF CLINICAL INVESTIGATION

mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling

(2011) V. S. Rodrik-Outmezguine et al.   Cancer Discovery

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

(2010) Gideon Bollag et al.   NATURE

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

(2009) Anurag Singh et al.   CANCER CELL

Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer

(2008) Arkaitz Carracedo et al.   JOURNAL OF CLINICAL INVESTIGATION

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 Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1

(2008) Y. Sancak et al.   SCIENCE