Targeting mutated GTPase KRAS in tumor therapies

Discovery of Novel Quinazoline-based Covalent Inhibitors of KRAS G12C with Various Cysteine-targeting Warheads as Potential Anticancer Agents

(2021) Ling Li et al.   BIOORGANIC CHEMISTRY

Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRASG12C

(2020) Jason G. Kettle et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition

(2020) Jenny Y. Xue et al.   NATURE

The KRAS-BCAA-BCAT2 axis in PDAC development

(2020) Mattia Falcone et al.   NATURE CELL BIOLOGY

Exon-4 Mutations in KRAS Affect MEK/ERK and PI3K/AKT Signaling in Human Multiple Myeloma Cell Lines

(2020) Susann Weißbach et al.   Cancers

Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer

(2020) Jay B. Fell et al.   JOURNAL OF MEDICINAL CHEMISTRY

High resolution crystal structure of a KRAS promoter G-quadruplex reveals a dimer with extensive poly-A π-stacking interactions for small-molecule recognition

(2020) Arnold Ou et al.   NUCLEIC ACIDS RESEARCH

CXCR2 signaling promotes secretory cancer‐associated fibroblasts in pancreatic ductal adenocarcinoma

(2020) Mohammad Awaji et al.   FASEB JOURNAL

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

(2020) Michael J. Bond et al.   ACS Central Science

BRAF and KRAS mutations in metastatic colorectal cancer: future perspectives for personalized therapy

(2020) Zi-Nan Li et al.   Gastroenterology Report

Targeting GCK pathway: a novel and selective therapeutic strategy against RAS mutated multiple myeloma

(2020) Shirong Li et al.   BLOOD

Oncogenic KRAS–expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice

(2020) Akiyoshi Kasuga et al.   CANCER SCIENCE

BI-3406, a potent and selective SOS1::KRAS interaction inhibitor, is effective in KRAS-driven cancers through combined MEK inhibition

(2020) Marco H Hofmann et al.   Cancer Discovery

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

(2020) Valerie Jentzsch et al.   Cancers

Design, synthesis and pharmacological evaluation of bicyclic and tetracyclic pyridopyrimidinone analogues as new KRASG12C inhibitors

(2020) Xuanzheng Xiao et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Small-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics

(2020) Hao Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation

(2019) Yoshihito Kano et al.   Nature Communications

Targeting the untargetable KRAS in cancer therapy

(2019) Pingyu Liu et al.   Acta Pharmaceutica Sinica B

Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer

(2019) Kirsten L. Bryant et al.   NATURE MEDICINE

Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer

(2019) Wantong Yao et al.   NATURE

The Combination of MEK inhibitor with Immunomodulatory Antibodies Targeting PD-1 and PD-L1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer

(2019) Jong Woo Lee et al.   Journal of Thoracic Oncology

The Role of KRAS in Endometrial Cancer: A Mini-Review

(2019) MICHAIL SIDERIS et al.   ANTICANCER RESEARCH

KRAS status is related to histological phenotype in gastric cancer: results from a large multicentre study

(2019) Lindsay C. Hewitt et al.   Gastric Cancer

Oncogenic Kras induces Nix-mediated mitophagy to promote pancreatic cancer

(2019) Timothy J Humpton et al.   Cancer Discovery

Vertical pathway inhibition overcomes adaptive feedback resistance to KRASG12C inhibition

(2019) Meagan B. Ryan et al.   CLINICAL CANCER RESEARCH

The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

(2019) Jude Canon et al.   NATURE

Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer

(2019) G. Aaron Hobbs et al.   Cancer Discovery

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

(2019) Jill Hallin et al.   Cancer Discovery

Exploiting RAS Nucleotide Cycling as a Strategy for Drugging RAS-Driven Cancers

(2019) Tyler E. Mattox et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors

(2019) Brian A. Lanman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting the Tumor Microenvironment: An Unexplored Strategy for Mutant KRAS Tumors

(2019) Patrícia Dias Carvalho et al.   Cancers

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

(2018) Matthew R. Janes et al.   CELL

Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment

(2018) Camilo E. Quevedo et al.   Nature Communications

OncogenicKrasdrives invasion and maintains metastases in colorectal cancer

(2017) Adam T. Boutin et al.   GENES & DEVELOPMENT

Endometrial Cancers With Activating KRas Mutations Have Activated Estrogen Signaling and Paradoxical Response to MEK Inhibition

(2017) Kari L. Ring et al.   INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER

Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

(2017) Ahmet Zehir et al.   NATURE MEDICINE

KRAS Mutation in Gastric Cancer and Prognostication Associated with Microsatellite Instability Status

(2017) Karol Polom et al.   PATHOLOGY & ONCOLOGY RESEARCH

KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer

(2017) Andrew M. Waters et al.   Cold Spring Harbor Perspectives in Medicine

IL6 Blockade Reprograms the Lung Tumor Microenvironment to Limit the Development and Progression of K-ras-Mutant Lung Cancer

(2016) M. S. Caetano et al.   CANCER RESEARCH

Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities

(2016) Barbara Bournet et al.   EUROPEAN JOURNAL OF CANCER

PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives

(2016) Vivek Asati et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The clinical significance of K-ras mutation in endometrial “surface epithelial changes” and their associated endometrial adenocarcinoma

(2016) Jinjun Xiong et al.   GYNECOLOGIC ONCOLOGY

MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade

(2016) Peter J.R. Ebert et al.   IMMUNITY

Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

(2016) Jonathan M. L. Ostrem et al.   NATURE REVIEWS DRUG DISCOVERY

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

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

KRAS Mutations in Mucinous Lesions of the Uterus

(2015) Mai He et al.   AMERICAN JOURNAL OF CLINICAL PATHOLOGY

The BRAF and MEK Inhibitors Dabrafenib and Trametinib: Effects on Immune Function and in Combination with Immunomodulatory Antibodies Targeting PD-1, PD-L1, and CTLA-4

(2015) L. Liu et al.   CLINICAL CANCER RESEARCH

Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma

(2015) Brian A. Walker et al.   JOURNAL OF CLINICAL ONCOLOGY

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

(2015) J. C. Hunter et al.   MOLECULAR CANCER RESEARCH

Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics

(2015) Kouji Banno et al.   JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH

Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells

(2014) S. W. Hofbauer et al.   BLOOD

Dragging Ras Back in the Ring

(2014) Andrew G. Stephen et al.   CANCER CELL

The clinical relevance of KRAS gene mutation in non-small-cell lung cancer

(2014) József Tímár   CURRENT OPINION IN ONCOLOGY

Whole genome gene copy number profiling of gastric cancer identifiesPAK1andKRASgene amplification as therapy targets

(2014) Ziliang Qian et al.   GENES CHROMOSOMES & CANCER

Targeting RAS–ERK signalling in cancer: promises and challenges

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

Drugging the undruggable RAS: Mission Possible?

(2014) Adrienne D. Cox 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

Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells

(2013) Klaus Okkenhaug   Annual Review of Immunology

Interleukin-6 Is Required for Pancreatic Cancer Progression by Promoting MAPK Signaling Activation and Oxidative Stress Resistance

(2013) Y. Zhang et al.   CANCER RESEARCH

The guanine nucleotide exchange factor Tiam1: A Janus-faced molecule in cellular signaling

(2013) P. Boissier et al.   CELLULAR SIGNALLING

Roles for KRAS in Pancreatic Tumor Development and Progression

(2013) Marina Pasca di Magliano et al.   GASTROENTEROLOGY

PTEN loss and KRAS activation cooperate in murine biliary tract malignancies

(2013) Victoria Marsh et al.   JOURNAL OF PATHOLOGY

Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase

(2013) Lei Gong et al.   Molecular Cancer

Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells

(2013) Cosimo Commisso et al.   NATURE

In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction

(2013) F. Shima et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NMR-based functional profiling of RASopathies and oncogenic RAS mutations

(2013) M. J. Smith et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation

(2012) Qi Sun et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Oncogenic Kras-Induced GM-CSF Production Promotes the Development of Pancreatic Neoplasia

(2012) Yuliya Pylayeva-Gupta et al.   CANCER CELL

A Comprehensive Survey of Ras Mutations in Cancer

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

Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism

(2012) Haoqiang Ying et al.   CELL

Is there a future for prenyltransferase inhibitors in cancer therapy?

(2012) Sarah A Holstein et al.   CURRENT OPINION IN PHARMACOLOGY

Association ofKRASG13D Tumor Mutations With Outcome in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy With or Without Cetuximab

(2012) Sabine Tejpar et al.   JOURNAL OF CLINICAL ONCOLOGY

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

Molecular pathology of lung cancer: key to personalized medicine

(2012) Liang Cheng et al.   MODERN PATHOLOGY

Prostaglandin E2 Regulates Pancreatic Stellate Cell Activity Via the EP4 Receptor

(2012) Chantale Charo et al.   PANCREAS

Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

(2012) T. Maurer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Stat3/Socs3 Activation by IL-6 Transsignaling Promotes Progression of Pancreatic Intraepithelial Neoplasia and Development of Pancreatic Cancer

(2011) Marina Lesina et al.   CANCER CELL

Pancreatic cancers require autophagy for tumor growth

(2011) S. Yang et al.   GENES & DEVELOPMENT

Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis

(2011) J. Y. Guo et al.   GENES & DEVELOPMENT

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

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

Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis

(2011) Gina M. DeNicola et al.   NATURE

Mutated RAS and constitutively activated Akt delineate distinct oncogenic pathways, which independently contribute to multiple myeloma cell survival

(2010) T. Steinbrunn et al.   BLOOD

RalGDS family members couple Ras to Ral signalling and that's not all

(2010) Elisa Ferro et al.   CELLULAR SIGNALLING

Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab

(2010) Wendy De Roock et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Allosteric modulation of Ras positions Q61 for a direct role in catalysis

(2010) G. Buhrman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting the RAF–MEK–ERK pathway in cancer therapy

(2009) Clara Montagut et al.   CANCER LETTERS

PKC and PLA2: Probing the complexities of the calcium network

(2009) Damian B. van Rossum et al.   CELL CALCIUM

Loss of Keap1 Function Activates Nrf2 and Provides Advantages for Lung Cancer Cell Growth

(2008) T. Ohta et al.   CANCER RESEARCH

Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints

(2008) D Llobet et al.   JOURNAL OF CLINICAL PATHOLOGY

Activated Kras, but Not Hras or Nras, May Initiate Tumors of Endodermal Origin via Stem Cell Expansion

(2008) M. P. Quinlan et al.   MOLECULAR AND CELLULAR BIOLOGY