KRAS: A Druggable Target in Colon Cancer Patients

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

(2021) Al B. Benson et al.   Journal of the National Comprehensive Cancer Network

Correlations Between Tumor Mutation Burden and Immunocyte Infiltration and Their Prognostic Value in Colon Cancer

(2021) Zhangjian Zhou et al.   Frontiers in Genetics

Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

(2021) Peijie Wu et al.   Frontiers in Cell and Developmental Biology

99O_PR KRYSTAL-1: Activity and preliminary pharmacodynamic (PD) analysis of adagrasib (MRTX849) in patients (Pts) with advanced non–small cell lung cancer (NSCLC) harboring KRASG12C mutation

(2021) G.J. Riely et al.   Journal of Thoracic Oncology

The origins and genetic interactions of KRAS mutations are allele- and tissue-specific

(2021) Joshua H. Cook et al.   Nature Communications

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

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

Clinical implementation and current advancement of blood liquid biopsy in cancer

(2021) Kazunori Watanabe et al.   JOURNAL OF HUMAN GENETICS

Acquired Resistance to KRASG12C Inhibition in Cancer

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

The impact of KRAS mutation, microsatellite instability, and tumor laterality on the prognosis of nonmetastatic colon cancer

(2021) Catherine G. Tran et al.   SURGERY

KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?

(2020) Misako Nagasaka et al.   CANCER TREATMENT REVIEWS

Neratinib degrades MST4 via autophagy that reduces membrane stiffness and is essential for the inactivation of PI3K, ERK1/2, and YAP/TAZ signaling

(2020) Paul Dent et al.   JOURNAL OF CELLULAR PHYSIOLOGY

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

(2020) Jenny Y. Xue et al.   NATURE

ERK/MAPK signalling pathway and tumorigenesis (Review)

(2020) Yan‑Jun Guo et al.   Experimental and Therapeutic Medicine

Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer

(2020) Ramesh K. Ramanathan et al.   Targeted Oncology

RAS-targeted therapies: is the undruggable drugged?

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

ERK signalling: a master regulator of cell behaviour, life and fate

(2020) Hugo Lavoie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Role of DNA Methylation in the Resistance to Therapy in Solid Tumors

(2020) Susana Romero-Garcia et al.   Frontiers in Oncology

KRAS: From undruggable to a druggable Cancer Target

(2020) Dipesh Uprety et al.   CANCER TREATMENT REVIEWS

SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling

(2020) Carmine Fedele et al.   JOURNAL OF EXPERIMENTAL MEDICINE

KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors

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

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

(2020) Marco Vacante et al.   Biomedicines

Targeting the untargetable KRAS in cancer therapy

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

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

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

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

Identification of a new inhibitor of KRAS-PDEδ interaction targeting KRAS mutant nonsmall cell lung cancer

(2019) Elaine Lai-Han Leung et al.   INTERNATIONAL JOURNAL OF CANCER

Impact of primary colorectal Cancer location on the KRAS status and its prognostic value

(2019) Ming-zhi Xie et al.   BMC GASTROENTEROLOGY

Belvarafenib, a novel pan-RAF inhibitor, in solid tumor patients harboring BRAF, KRAS, or NRAS mutations: Phase I study.

(2019) Tae Won Kim et al.   JOURNAL OF CLINICAL ONCOLOGY

Uncommon mutational profiles of metastatic colorectal cancer detected during routine genotyping using next generation sequencing

(2019) Claire Franczak et al.   Scientific Reports

Analysis of KRAS , NRAS , BRAF , PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients

(2019) Francesco Sclafani et al.   INTERNATIONAL JOURNAL OF CANCER

RAS mutations in human cancers: Roles in precision medicine

(2019) Avaniyapuram Kannan Murugan et al.   SEMINARS IN CANCER BIOLOGY

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

(2019) Miriam Molina-Arcas et al.   Science Translational Medicine

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

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

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

(2018) Matthew R. Janes et al.   CELL

COP1/DET1/ETS axis regulates ERK transcriptome and sensitivity to MAPK inhibitors

(2018) Yuanyuan Xie et al.   JOURNAL OF CLINICAL INVESTIGATION

Afatinib restrains K-RAS–driven lung tumorigenesis

(2018) Herwig P. Moll et al.   Science Translational Medicine

The ERBB network facilitates KRAS-driven lung tumorigenesis

(2018) Björn Kruspig et al.   Science Translational Medicine

Differential Effector Engagement by Oncogenic KRAS

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

Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology

(2018) Shuji Ogino et al.   Annual Review of Pathology-Mechanisms of Disease

Role of liquid biopsies in colorectal cancer

(2018) Beatriz Wills et al.   CURRENT PROBLEMS IN CANCER

Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology

(2018) Matthias Gehringer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Therapeutic strategies to target RAS-mutant cancers

(2018) Meagan B. Ryan et al.   Nature Reviews Clinical Oncology

Targeting the α4–α5 dimerization interface of K-RAS inhibits tumor formation in vivo

(2018) Imran Khan et al.   ONCOGENE

Rechallenge for Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer With Acquired Resistance to First-line Cetuximab and Irinotecan

(2018) Chiara Cremolini et al.   JAMA Oncology

Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA

(2017) Matthew A. Coelho et al.   IMMUNITY

Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study

(2017) Michael J Overman et al.   LANCET ONCOLOGY

Inhibition of Isoprenylcysteine Carboxylmethyltransferase Induces Cell-Cycle Arrest and Apoptosis through p21 and p21-Regulated BNIP3 Induction in Pancreatic Cancer

(2017) Kanjoormana Aryan Manu et al.   MOLECULAR CANCER THERAPEUTICS

Elements of cancer immunity and the cancer–immune set point

(2017) Daniel S. Chen et al.   NATURE

Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

(2017) Dung T. Le et al.   SCIENCE

Drugging RAS: Know the enemy

(2017) Bjoern Papke et al.   SCIENCE

A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy

(2017) May Cho et al.   Oncotarget

ICECREAM: randomised phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic colorectal cancer with either KRAS, NRAS, BRAF and PI3KCA wild type, or G13D mutated tumours

(2016) Eva Segelov et al.   BMC CANCER

Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis

(2016) Tsuyoshi Hamada et al.   JOURNAL OF GASTROENTEROLOGY

K-Ras protein as a drug target

(2016) Frank McCormick   JOURNAL OF MOLECULAR MEDICINE-JMM

Inhibition of RAS function through targeting an allosteric regulatory site

(2016) Russell Spencer-Smith et al.   Nature Chemical Biology

T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer

(2016) Eric Tran et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

(2016) P. Lito et al.   SCIENCE

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

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

Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors

(2015) A. Patnaik et al.   CLINICAL CANCER RESEARCH

Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers

(2015) E.M.V. de Cuba et al.   INTERNATIONAL JOURNAL OF CANCER

Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin

(2015) Matthew G Oser et al.   LANCET ONCOLOGY

Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients

(2015) Giulia Siravegna et al.   NATURE MEDICINE

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

(2015) Dung T. Le et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

GTP-Dependent K-Ras Dimerization

(2015) Serena Muratcioglu et al.   STRUCTURE

RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

(2015) Talia Golan et al.   Oncotarget

Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors

(2015) Q. J. Wang et al.   Cancer Immunology Research

ExtendedRASmutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials

(2014) M. J. Sorich et al.   ANNALS OF ONCOLOGY

KRAS Mutation is Associated with Worse Prognosis in Stage III or High-risk Stage II Colon Cancer Patients Treated with Adjuvant FOLFOX

(2014) Dae-Won Lee et al.   ANNALS OF SURGICAL ONCOLOGY

A Phase Ib Dose-Escalation Study of the Oral Pan-PI3K Inhibitor Buparlisib (BKM120) in Combination with the Oral MEK1/2 Inhibitor Trametinib (GSK1120212) in Patients with Selected Advanced Solid Tumors

(2014) P. L. Bedard et al.   CLINICAL CANCER RESEARCH

Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients

(2014) Roy S. Herbst et al.   NATURE

Histological transformation from non-small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor

(2014) Woo-Jin Kim et al.   Thoracic Cancer

Inflammatory networks and immune surveillance of pancreatic carcinoma

(2013) Robert H Vonderheide et al.   CURRENT OPINION IN IMMUNOLOGY

Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention

(2013) Dora Colussi et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

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

(2013) Jonathan M. Ostrem et al.   NATURE

Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

(2013) Gunther Zimmermann et al.   NATURE

Signatures of mutational processes in human cancer

(2013) Ludmil B. Alexandrov et al.   NATURE

Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer

(2013) Jean-Yves Douillard et al.   NEW ENGLAND JOURNAL OF 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

A patient with simultaneously appearing adenocarcinoma and small-cell lung carcinoma harbouring an identical EGFR exon 19 mutation

(2012) S. van Riel et al.   ANNALS OF ONCOLOGY

Resistance to BRAF Inhibition in BRAF-Mutant Colon Cancer Can Be Overcome with PI3K Inhibition or Demethylating Agents

(2012) M. Mao et al.   CLINICAL CANCER RESEARCH

Mutant KRAS Codon 12 and 13 Alleles in Patients With Metastatic Colorectal Cancer: Assessment As Prognostic and Predictive Biomarkers of Response to Panitumumab

(2012) Marc Peeters et al.   JOURNAL OF CLINICAL ONCOLOGY

Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer

(2012) Sandra Misale et al.   NATURE

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

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

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

Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

(2011) Gordon Hutchins et al.   JOURNAL OF CLINICAL ONCOLOGY

Lack of Correlation between Epidermal Growth Factor Receptor Status and Response to Panitumumab Monotherapy in Metastatic Colorectal Cancer

(2010) J. R. Hecht et al.   CLINICAL CANCER RESEARCH

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

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

(2010) Poulikos I. Poulikakos et al.   NATURE

RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

(2010) Georgia Hatzivassiliou et al.   NATURE

Inhibition of isoprenylcysteine carboxylmethyltransferase induces autophagic-dependent apoptosis and impairs tumor growth

(2010) M Wang et al.   ONCOGENE

PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers

(2009) S. Wee et al.   CANCER RESEARCH

K-Ras Mutations and Treatment Outcome in Colorectal Cancer Patients Receiving Exclusive Fluoropyrimidine Therapy

(2008) M.-C. Etienne-Grimaldi et al.   CLINICAL CANCER RESEARCH

Wild-TypeKRASIs Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer

(2008) Rafael G. Amado et al.   JOURNAL OF CLINICAL 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

Circulating mutant DNA to assess tumor dynamics

(2008) Frank Diehl et al.   NATURE MEDICINE

K-rasMutations and Benefit from Cetuximab in Advanced Colorectal Cancer

(2008) Christos S. Karapetis et al.   NEW ENGLAND JOURNAL OF MEDICINE