Drugging KRAS: current perspectives and state-of-art review

First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: A phase I/II study evaluating efficacy and safety

(2022) John H Strickler et al.   JOURNAL OF CLINICAL ONCOLOGY

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1)

(2022) Sai-Hong Ignatius Ou et al.   JOURNAL OF CLINICAL ONCOLOGY

Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants

(2022) Marco H. Hofmann et al.   Cancer Discovery

Concomitant KRAS mutations attenuate sensitivity of non-small cell lung cancer cells to KRAS G12C inhibition

(2022) Tereza Vaclova et al.   Scientific Reports

Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non–Small Cell Lung Cancer

(2022) Joshua K. Sabari et al.   CLINICAL CANCER RESEARCH

Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRASG12D mutated non-small cell lung cancer

(2022) B. Ricciuti et al.   ANNALS OF ONCOLOGY

Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S)

(2022) Ziyang Zhang et al.   Nature Chemical Biology

Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation

(2022) Pasi A. Jänne et al.   NEW ENGLAND JOURNAL OF MEDICINE

Therapeutic KRAS G12C inhibition drives effective interferon-mediated antitumor immunity in immunogenic lung cancers

(2022) Edurne Mugarza et al.   Science Advances

LBA10 Sotorasib versus docetaxel for previously treated non-small cell lung cancer with KRAS G12C mutation: CodeBreaK 200 phase III study

(2022) M.L. Johnson et al.   ANNALS OF ONCOLOGY

Chemoselective Covalent Modification of K-Ras(G12R) with a Small Molecule Electrophile

(2022) Ziyang Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

OA03.06 CodeBreaK 100/101: First Report of Safety/Efficacy of Sotorasib in Combination with Pembrolizumab or Atezolizumab in Advanced KRAS p.G12C NSCLC

(2022) B.T. Li et al.   Journal of Thoracic Oncology

OA03.03 Sotorasib in Combination with RMC-4630, a SHP2 Inhibitor, in KRAS p.G12C-Mutated NSCLC and Other Solid Tumors

(2022) G. Falchook et al.   Journal of Thoracic Oncology

Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients

(2021) Jungang Liu et al.   Journal of Translational Medicine

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms

(2021) Ye Wang et al.   Scientific Reports

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

(2021) Hyuna Sung et al.   CA-A CANCER JOURNAL FOR CLINICIANS

KRAS mutation in pancreatic cancer

(2021) Ji Luo   SEMINARS IN ONCOLOGY

Correction to: Lonafarnib: First Approval

(2021) Sohita Dhillon   DRUGS

Genetic Determinants of Outcome in Intrahepatic Cholangiocarcinoma

(2021) Thomas Boerner et al.   HEPATOLOGY

Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations

(2021) Alan L. Ho et al.   JOURNAL OF CLINICAL ONCOLOGY

The KRASG12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy

(2021) David M. Briere et al.   MOLECULAR CANCER THERAPEUTICS

Clinical acquired resistance to KRASG12C inhibition through a novel KRAS switch-II pocket mutation and polyclonal alterations converging on RAS-MAPK reactivation

(2021) Noritaka Tanaka et al.   Cancer Discovery

KRAS Mutation Dictates the Cancer Immune Environment in Pancreatic Ductal Adenocarcinoma and Other Adenocarcinomas

(2021) Meichen Gu et al.   Cancers

LBA6 KRYSTAL-1: Adagrasib (MRTX849) as monotherapy or combined with cetuximab (Cetux) in patients (Pts) with colorectal cancer (CRC) harboring a KRASG12C mutation

(2021) J. Weiss et al.   ANNALS OF ONCOLOGY

524P A phase I, open-label, dose-escalation trial of BI 1701963 in patients (pts) with KRAS mutated solid tumours: A snapshot analysis

(2021) M.L. Johnson et al.   ANNALS OF ONCOLOGY

434P CodeBreaK 101 subprotocol H: Phase Ib study evaluating combination of sotorasib (Soto), a KRASG12C inhibitor, and panitumumab (PMab), an EGFR inhibitor, in advanced KRAS p.G12C-mutated colorectal cancer (CRC)

(2021) M. Fakih et al.   ANNALS OF ONCOLOGY

KRAS inhibitor-resistance in MET-amplified KRASG12C non-small cell lung cancer induced by RAS- and non-RAS-mediated cell signaling mechanisms

(2021) Shinichiro Suzuki et al.   CLINICAL CANCER RESEARCH

Overall survival and exploratory subgroup analyses from the phase 2 CodeBreaK 100 trial evaluating sotorasib in pretreated KRAS p.G12C mutated non-small cell lung cancer.

(2021) Ferdinandos Skoulidis et al.   JOURNAL OF CLINICAL ONCOLOGY

Binimetinib, pemetrexed and cisplatin, followed by maintenance of binimetinib and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) and KRAS mutations. The phase 1B SAKK 19/16 trial

(2021) Patrizia Froesch et al.   LUNG CANCER

Characterization of KRAS Mutation Subtypes in Non-Small Cell Lung Cancer

(2021) Julia Judd et al.   MOLECULAR CANCER THERAPEUTICS

Sotorasib for Lung Cancers with KRAS p.G12C Mutation

(2021) Ferdinandos Skoulidis et al.   NEW ENGLAND JOURNAL OF MEDICINE

Acquired Resistance to KRASG12C Inhibition in Cancer

(2021) Mark M. Awad et al.   NEW ENGLAND JOURNAL OF MEDICINE

Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK–YAP Signaling

(2021) Baoyuan Zhang et al.   Advanced Science

Identification of MRTX1133, a Noncovalent, Potent, and Selective KRASG12D Inhibitor

(2021) Xiaolun Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial

(2021) Marwan G Fakih et al.   LANCET ONCOLOGY

Diverse alterations associated with resistance to KRAS(G12C) inhibition

(2021) Yulei Zhao et al.   NATURE

Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status

(2021) Biagio Ricciuti et al.   Journal of Thoracic Oncology

A12 The SHP2 Inhibitor RMC-4630 in Patients with KRAS-Mutant Non-Small Cell Lung Cancer: Preliminary Evaluation of a First-in-Man Phase 1 Clinical Trial

(2020) S.I. Ou et al.   Journal of Thoracic Oncology

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

(2020) Jenny Y. Xue et al.   NATURE

Resistance looms for KRASG12C inhibitors

(2020) Aaron N. Hata et al.   NATURE MEDICINE

KRAS as a druggable target in NSCLC: Rising like a phoenix after decades of development failures

(2020) Alex Friedlaender et al.   CANCER TREATMENT REVIEWS

Phase I dose-finding study of oral ERK1/2 inhibitor LTT462 in patients (pts) with advanced solid tumors harboring MAPK pathway alterations.

(2020) Filip Janku et al.   JOURNAL OF CLINICAL ONCOLOGY

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

EGFR blockade reverts resistance to KRAS G12C inhibition in colorectal cancer

(2020) Vito Amodio et al.   Cancer Discovery

The effects of mutant Ras proteins on the cell signalome

(2020) Tamás Takács et al.   CANCER AND METASTASIS REVIEWS

RAS-targeted therapies: is the undruggable drugged?

(2020) Amanda R. Moore et al.   NATURE REVIEWS DRUG DISCOVERY

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

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

Combinations with allosteric SHP2 inhibitor TNO155 to block receptor tyrosine kinase signaling

(2020) Huai-Xiang Hao et al.   CLINICAL CANCER RESEARCH

Epithelial-to-Mesenchymal Transition is a Cause of Both Intrinsic and Acquired Resistance to KRAS G12C Inhibitor in KRAS G12C–Mutant Non–Small Cell Lung Cancer

(2020) Yuta Adachi et al.   CLINICAL CANCER RESEARCH

KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors

(2020) David S. Hong et al.   NEW ENGLAND JOURNAL OF MEDICINE

One Step at a Time — Clinical Evidence That KRAS Is Indeed Druggable

(2020) Patricia M. LoRusso et al.   NEW ENGLAND JOURNAL OF MEDICINE

STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world

(2020) Norah J. Shire et al.   PLoS One

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

A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER

(2020) Jonathan W. Goldman et al.   Frontiers in Oncology

Genetic Alterations of Metastatic Colorectal Cancer

(2020) Ugo Testa et al.   Biomedicines

Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction

(2019) Roman C. Hillig et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers

(2019) Conan G. Kinsey et al.   NATURE MEDICINE

KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer

(2019) Wenting Liao et al.   CANCER CELL

A phase I dose escalation (DE) study of ERK inhibitor, LY3214996, in advanced (adv) cancer (CA) patients (pts).

(2019) Shubham Pant et al.   JOURNAL OF CLINICAL ONCOLOGY

K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways

(2019) Matthias Scheffler et al.   Journal of Thoracic Oncology

Drugging an undruggable pocket on KRAS

(2019) Dirk Kessler et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Durvalumab With or Without Tremelimumab for Patients With Metastatic Pancreatic Ductal Adenocarcinoma

(2019) Eileen M. O’Reilly et al.   JAMA Oncology

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

KRAS G13D sensitivity to neurofibromin-mediated GTP hydrolysis

(2019) Dana Rabara et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer

(2018) Rona Yaeger et al.   CANCER CELL

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

(2018) Matthew R. Janes et al.   CELL

Oncogenic Signaling Pathways in The Cancer Genome Atlas

(2018) Francisco Sanchez-Vega et al.   CELL

Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase

(2018) Dietrich A. Ruess et al.   NATURE MEDICINE

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

(2018) Sara Mainardi et al.   NATURE MEDICINE

Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C

(2018) Vincent L. Cannataro et al.   ONCOGENE

STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma

(2018) Ferdinandos Skoulidis et al.   Cancer Discovery

RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers

(2018) Robert J. Nichols et al.   NATURE CELL BIOLOGY

SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models

(2018) Carmine Fedele et al.   Cancer Discovery

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

(2018) Mingxia Zhao et al.   Acta Pharmaceutica Sinica B

Effect Of Coexisting Kras And Tp53 Mutations In Patients Treated With Chemotherapy For Non-Small Cell Lung Cancer

(2018) Pascale Tomasini et al.   Clinical Lung Cancer

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

Integrated genomic characterization of oesophageal carcinoma

(2017)   NATURE

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

(2017) Ahmet Zehir et al.   NATURE MEDICINE

Survival of pancreatic cancer cells lacking KRAS function

(2017) Mandar Deepak Muzumdar et al.   Nature Communications

Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer

(2017) Yelena Y. Janjigian et al.   Cancer Discovery

First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study

(2017) Ryan J. Sullivan et al.   Cancer Discovery

Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma

(2017) Apinya Jusakul et al.   Cancer Discovery

KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer

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

Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression

(2016) Tikvah K. Hayes et al.   CANCER CELL

Negative feedback regulation of the ERK1/2 MAPK pathway

(2016) David Lake et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

(2016) Ying-Nan P. Chen et al.   NATURE

Genomic analyses identify molecular subtypes of pancreatic cancer

(2016) Peter Bailey et al.   NATURE

Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas

(2016) Joshua D Campbell et al.   NATURE GENETICS

Covalent Guanosine Mimetic Inhibitors of G12C KRAS

(2016) Yuan Xiong et al.   ACS Medicinal Chemistry Letters

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

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

Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors

(2016) A. Patnaik et al.   Cancer Discovery

Contribution of KRAS mutations and c.2369C > T (p.T790M) EGFR to acquired resistance to EGFR-TKIs in EGFR mutant NSCLC: a study on circulating tumor DNA

(2016) Marzia Del Re et al.   Oncotarget

Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

(2016) Marios Giannakis et al.   Cell Reports

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

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

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

Ras-GTP dimers activate the Mitogen-Activated Protein Kinase (MAPK) pathway

(2015) Xiaolin Nan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Disruption of CRAF-Mediated MEK Activation Is Required for Effective MEK Inhibition in KRAS Mutant Tumors

(2014) Piro Lito et al.   CANCER CELL

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

Downstream of Mutant KRAS, the Transcription Regulator YAP Is Essential for Neoplastic Progression to Pancreatic Ductal Adenocarcinoma

(2014) W. Zhang et al.   Science Signaling

Therapeutic Targeting of Oncogenic K-Ras by a Covalent Catalytic Site Inhibitor

(2013) Sang Min Lim et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

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

(2013) Jonathan M. Ostrem et al.   NATURE

Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas

(2012) Piro Lito et al.   CANCER CELL

Molecular Epidemiology of EGFR and KRAS Mutations in 3,026 Lung Adenocarcinomas: Higher Susceptibility of Women to Smoking-Related KRAS-Mutant Cancers

(2012) S. Dogan et al.   CLINICAL CANCER RESEARCH

Mechanisms of Resistance to Crizotinib in Patients withALKGene Rearranged Non–Small Cell Lung Cancer

(2012) Robert C. Doebele et al.   CLINICAL CANCER RESEARCH

Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

(2012) Tadashi Yokosuka et al.   JOURNAL OF EXPERIMENTAL MEDICINE

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

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

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

(2012) Anirudh Prahallad et al.   NATURE

STAT3 Plays a Critical Role in KRAS-Induced Pancreatic Tumorigenesis

(2011) R. B. Corcoran et al.   CANCER RESEARCH

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

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

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

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

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

(2009) Anurag Singh et al.   CANCER CELL

Molecular Basis of Colorectal Cancer

(2009) Sanford D. Markowitz et al.   NEW ENGLAND JOURNAL OF MEDICINE

Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor

(2008) A. J. Gonzales et al.   MOLECULAR CANCER THERAPEUTICS

The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway

(2007) Marie Dance et al.   CELLULAR SIGNALLING