4.6 Review

The current state of the art and future trends in RAS-targeted cancer therapies

Related references

Note: Only part of the references are listed.
Editorial Material Chemistry, Medicinal

PROTAC cell permeability and oral bioavailability: a journey into uncharted territory

Vasanthanathan Poongavanam et al.

FUTURE MEDICINAL CHEMISTRY (2022)

Article Oncology

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

Sai-Hong Ignatius Ou et al.

Summary: This study reported the results of a clinical trial using adagrasib to treat non-small-cell lung cancer, colorectal cancer, and other solid tumors with the KRAS(G12C) mutation. The recommended phase II dose was identified as 600 mg twice a day, and it demonstrated good tolerability and antitumor activity.

JOURNAL OF CLINICAL ONCOLOGY (2022)

Article Oncology

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

Marwan G. Fakih et al.

Summary: Sotorasib, a specific inhibitor of KRAS(G12C) protein, showed modest anti-tumour activity and manageable safety in heavily pretreated patients with colorectal cancer in a phase 2 trial. The overall response rate of 9.7% did not reach the benchmark, but sotorasib is being evaluated in combination with other therapeutics to enhance potential activity and address potential resistance mechanisms.

LANCET ONCOLOGY (2022)

Article Medicine, General & Internal

Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection

Victoria Hall et al.

Summary: This study investigated the duration and effectiveness of immunity among healthcare workers in the United Kingdom. It found that two doses of the BNT162b2 vaccine provided high short-term protection against SARS-CoV-2 infection, but this protection significantly decreased after six months. However, infection-acquired immunity boosted by vaccination remained high, even more than one year after infection.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Article Oncology

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

Biagio Ricciuti et al.

Summary: STK11 and KEAP1 mutations have a negative impact on the efficacy of immunotherapy in lung adenocarcinoma, but this effect is only observed in KRAS-positive tumors. Tumors with concurrent KRAS/STK11 and KRAS/KEAP1 mutations exhibit distinct immune characteristics.

JOURNAL OF THORACIC ONCOLOGY (2022)

Article Oncology

Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts

Vania Vidimar et al.

Summary: This study demonstrates the anticancer activity of RRSP-DTB in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) cell lines and patient-derived xenografts (PDX). RRSP-DTB effectively inhibits cell proliferation and induces tumor regression with disrupted tissue architecture, increased fibrosis, and reduced phospho-ERK levels. The study suggests the potential of RRSP-DTB as a promising therapeutic option for RAS-addicted tumors.

MOLECULAR CANCER THERAPEUTICS (2022)

Article Biochemistry & Molecular Biology

KRAS is vulnerable to reversible switch-II pocket engagement in cells

James D. Vasta et al.

Summary: Current small-molecule inhibitors can selectively bind to the SII-P of KRAS, providing a viable approach for treating KRAS-driven cancer and unveiling new therapeutic opportunities.

NATURE CHEMICAL BIOLOGY (2022)

Article Oncology

Combined Inhibition of SHP2 and CXCR1/2 Promotes Antitumor T-cell Response in NSCLC

Kwan Ho Tang et al.

Summary: Our study suggests that inhibiting the SHP2/RAS/ERK pathway leads to upregulation of CXCR2 ligands and recruitment of S100A8 hi gMDSCs, suppressing T cells in non-small cell lung cancer. Combining SHP2/CXCR2 inhibitors can block gMDSC immigration, enhance Th1 polarization, induce highly cytotoxic CD8 + KLRG1 + effector T cells, and improve survival.

CANCER DISCOVERY (2022)

Article Medicine, General & Internal

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

Pasi A. Jaenne et al.

Summary: Adagrasib demonstrated clinical efficacy without new safety signals in previously treated KRAS(G12C)-mutated NSCLC patients.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Article Immunology

SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling

Carmine Fedele et al.

Summary: The combination of SHP2 inhibitor and KRAS (G12C) inhibitor shows significant survival benefits in PDAC and NSCLC, inducing favorable changes in the tumor microenvironment by reducing myeloid suppressor cells, increasing CD8(+) T cells, and enhancing sensitivity to PD-1 blockade.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

Article Oncology

BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition

Marco H. Hofmann et al.

Summary: Inhibiting SOS1, a KRAS activator and important feedback node, is an effective approach to treat KRAS-driven cancers. The highly potent and selective small-molecule SOS1 inhibitor, BI-3406, reduces cellular proliferation of KRAS-driven cancers by preventing the interaction with KRAS. Combination of SOS1 and MEK inhibition represents a novel and effective therapeutic concept for addressing KRAS-driven tumors.

CANCER DISCOVERY (2021)

Editorial Material Biochemistry & Molecular Biology

The Rise of Molecular Glues

Stuart L. Schreiber

Summary: The 30th anniversary of the discovery of cyclosporin A and FK506 marks a milestone in understanding their role as molecular glues that induce new protein-protein interactions. The emergence of new molecular-glue probes and medications has sparked interest in this field.
Letter Medicine, General & Internal

Distribution of KRASG12C Somatic Mutations across Race, Sex, and Cancer Type

Amin H. Nassar et al.

Summary: A survey of over 32,000 cancers in the GENIE registry found differences in distribution of KRAS(G12C) mutations in various cancer types and between men and women of different races. As agents capable of targeting specific mutant alleles like sotorasib become available, tumor mutation analysis is becoming increasingly important in treatment selection.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Editorial Material Oncology

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report

Qinghan Liu et al.

Summary: This case report describes a patient with lung adenocarcinoma who developed adenosquamous carcinoma and EGFR mutations. Through surgical intervention and new drug treatment, the patient's current overall survival is 60 months.

TUMORI JOURNAL (2021)

Article Chemistry, Multidisciplinary

Exquisitely Specific anti-KRAS Biodegraders Inform on the Cellular Prevalence of Nucleotide-Loaded States

Shuhui Lim et al.

Summary: Mutations in RAS proteins are common drivers of cancer, with some mutations being particularly difficult to treat. Targeted degradation has emerged as a promising alternative approach, but challenges remain in finding high-affinity ligands for KRAS and in discovering hybrid molecules that can effectively degrade the protein.

ACS CENTRAL SCIENCE (2021)

Article Chemistry, Medicinal

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

Xiaolun Wang et al.

Summary: KRAS(G12D), the most common oncogenic KRAS mutation, is a promising target for solid tumor treatment. Selective inhibition of KRAS(G12C) presents a significant challenge due to the requirement of high affinity inhibitors to bind the mutant protein. The discovery of the noncovalent, potent, and selective KRAS(G12C) inhibitor MRTX1133, shown to be efficacious in a mouse tumor model, represents a significant advancement in the field.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Multidisciplinary Sciences

Diverse alterations associated with resistance to KRAS(G12C) inhibition

Yulei Zhao et al.

Summary: Resistance to KRAS(G12C) inhibitors demonstrates a heterogeneous pattern with multiple subclonal events emerging during treatment. Co-targeting of ERK signaling intermediates can enhance the antiproliferative effect of G12C inhibitor treatment in models with acquired RAS or BRAF mutations.

NATURE (2021)

Article Oncology

Non-Small Cell Lung Cancer, Version 2.2021 Featured Updates to the NCCN Guidelines

David S. Ettinger et al.

Summary: The NCCN Guidelines for NSCLC cover all aspects of management, with recent updates focusing on targeted therapies, immunotherapies, and their respective biomarkers.

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK (2021)

Article Multidisciplinary Sciences

The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS

Chuanchuan Li et al.

Summary: This study reveals that RGS3 enhances the GTPase activity of both mutant and wild-type KRAS proteins, leading to the inactivation of KRAS and explaining its vulnerability to emerging clinically effective therapies.

SCIENCE (2021)

Article Multidisciplinary Sciences

KRAS drives immune evasion in a genetic model of pancreatic cancer

Irene Ischenko et al.

Summary: In established KRAS-driven pancreatic cancer, KRAS ablation does not impact intrinsic tumorigenic capacity but triggers an antitumor immune response, highlighting the significance of KRAS-driven immune suppression in tumor maintenance.

NATURE COMMUNICATIONS (2021)

Article Oncology

Cytotoxicity of combinations of the pan-KRAS inhibitor BAY-293 against primary non-small lung cancer cells

Adelina Plangger et al.

Summary: The study demonstrates that combination therapy of BAY-293 with various drugs shows cytotoxicity against Osimertinib-resistant NSCLC cell lines, potentially improving treatment outcomes by interfering with downstream signaling pathways.

TRANSLATIONAL ONCOLOGY (2021)

Article Multidisciplinary Sciences

The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors

Teklab Gebregiworgis et al.

Summary: This study demonstrates that KRAS Q61H mutation is not regulated by SHP2, leading to insensitivity to SHP2 inhibitors in pancreatic cancer cells. Furthermore, cancer cells with different KRAS mutations exhibit variable sensitivity to SHP2 inhibitors, potentially due to differences in regulation by GAP and GEF activities, as well as binding affinity to RAF.

NATURE COMMUNICATIONS (2021)

Article Multidisciplinary Sciences

Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry

Febe van Maldegem et al.

Summary: This study introduces a workflow for studying the TME in mouse models using imaging mass cytometry, allowing for optimized image segmentation strategies and automated processes for parallel segmentation of large multi-image datasets.

NATURE COMMUNICATIONS (2021)

Article Immunology

Bispecific antibodies targeting mutant RAS neoantigens

Jacqueline Douglass et al.

Summary: The study isolated specific single-chain variable fragments targeting mutations in the RAS oncogenes. By developing an immunotherapeutic agent capable of killing cancer cells expressing very low levels of RAS-derived antigens, the researchers demonstrated the potential for more specific anticancer therapeutics. The use of CRISPR-mediated alterations provided strong genetic evidence for the specificity of the developed immunotherapeutic agent.

SCIENCE IMMUNOLOGY (2021)

Article Oncology

KRAS Secondary Mutations That Confer Acquired Resistance to KRAS G12C Inhibitors, Sotorasib and Adagrasib, and Overcoming Strategies: Insights From In Vitro Experiments

Takamasa Koga et al.

Summary: The study developed in vitro models of KRAS G12C cancer resistant to sotorasib and adagrasib, and found that most clones harbored secondary KRAS mutations which showed differential sensitivity to the inhibitors. Sequential use of sotorasib and adagrasib may be considered in some cases, while a combination of BI-3406 and trametinib could be an effective strategy to overcome resistance caused by secondary Y96D and Y96S mutations.

JOURNAL OF THORACIC ONCOLOGY (2021)

Article Oncology

ES28.04 Emerging Mechanisms to Target KRAS Directly

M. Nagasaka

Journal of Thoracic Oncology (2021)

Article Oncology

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

David M. Briere et al.

Summary: KRAS inhibition can reverse an immunosuppressive tumor microenvironment and sensitize tumors to checkpoint inhibitor therapy (CIT) through multiple mechanisms.

MOLECULAR CANCER THERAPEUTICS (2021)

Article Oncology

Clinical Acquired Resistance to KRASG12C Inhibition through a novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS-MAPK Reactivation

Noritaka Tanaka et al.

Summary: This study described a patient with KRAS(G12C) non-small cell lung cancer who developed polyclonal acquired resistance to MRTX849 treatment. The research identified 10 heterogeneous resistance alterations that converged to reactivate the RAS-MAPK signaling pathway. Additionally, a novel KRAS(Y96D) mutation affecting key protein-drug interactions and driving resistance was discovered.

CANCER DISCOVERY (2021)

Article Medicine, General & Internal

Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma

Paul Nathan et al.

Summary: The randomized trial of tebentafusp for metastatic uveal melanoma showed a higher 1-year overall survival rate among patients who received tebentafusp compared to those who received the investigator's choice of therapy, indicating superior efficacy.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Medicine, General & Internal

Acquired Resistance to KRASG12C Inhibition in Cancer

M. M. Awad et al.

Summary: A study of 38 patients with KRAS(G12C)-mutant cancers treated with adagrasib revealed diverse mechanisms of acquired resistance in 45% of them, including various mutations and bypass mechanisms. New therapeutic strategies are needed to overcome this drug resistance.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Oncology

Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition

Meagan B. Ryan et al.

CLINICAL CANCER RESEARCH (2020)

Article Multidisciplinary Sciences

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

Jenny Y. Xue et al.

NATURE (2020)

Letter Multidisciplinary Sciences

The small molecule BI-2852 induces a nonfunctional dimer of KRAS

Timothy H. Tran et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Review Oncology

The Frequency of Ras Mutations in Cancer

Ian A. Prior et al.

CANCER RESEARCH (2020)

Article Multidisciplinary Sciences

Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I

Keisuke Yamamoto et al.

NATURE (2020)

Review Cell Biology

Guidelines and definitions for research on epithelial-mesenchymal transition

Jing Yang et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

Article Chemistry, Multidisciplinary

Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs

Michael J. Bond et al.

ACS CENTRAL SCIENCE (2020)

Article Multidisciplinary Sciences

A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS

Nicolas Bery et al.

NATURE COMMUNICATIONS (2020)

Article Multidisciplinary Sciences

KRAS(G12C)-AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations

Tatu Pantsar

SCIENTIFIC REPORTS (2020)

Article Medicine, General & Internal

KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors

David S. Hong et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Chemistry, Multidisciplinary

GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf

Ziyang Zhang et al.

ACS CENTRAL SCIENCE (2020)

Review Medicine, General & Internal

Systemic Therapy for Estrogen Receptor-Positive, HER2-Negative Breast Cancer

Harold J. Burstein

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Review Biochemistry & Molecular Biology

The current understanding of KRAS protein structure and dynamics

Tatu Pantsar

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2020)

Article Biochemistry & Molecular Biology

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

Conan G. Kinsey et al.

NATURE MEDICINE (2019)

Article Multidisciplinary Sciences

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

Roman C. Hillig et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Article Pharmacology & Pharmacy

CD44 targeted delivery of siRNA by using HA-decorated nanotechnologies for KRAS silencing in cancer treatment

A. Tirella et al.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2019)

Article Biochemistry & Molecular Biology

KRASG12C inhibition produces a driver-limited state revealing collateral dependencies

Kevin Lou et al.

SCIENCE SIGNALING (2019)

Article Chemistry, Multidisciplinary

Targeting KRAS Mutant Lung Cancer Cells with siRNA-Loaded Bovine Serum Albumin Nanoparticles

Aditi Mehta et al.

PHARMACEUTICAL RESEARCH (2019)

Article Multidisciplinary Sciences

Drugging an undruggable pocket on KRAS

Dirk Kessler et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Review Oncology

RAS: Striking at the Core of the Oncogenic Circuitry

Ryan C. Gimple et al.

FRONTIERS IN ONCOLOGY (2019)

Review Oncology

New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness

Haitang Yang et al.

FRONTIERS IN ONCOLOGY (2019)

Article Chemistry, Multidisciplinary

Bifunctional Small-Molecule Ligands of K-Ras Induce Its Association with Immunophilin Proteins

Ziyang Zhang et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2019)

Article Multidisciplinary Sciences

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

Jude Canon et al.

NATURE (2019)

Review Pharmacology & Pharmacy

Pharmacological targeting of RAS: Recent success with direct inhibitors

John P. O'Bryan

PHARMACOLOGICAL RESEARCH (2019)

Review Oncology

Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy

Ferdinandos Skoulidis et al.

NATURE REVIEWS CANCER (2019)

Article Biochemistry & Molecular Biology

Exceptionally high-affinity Ras binders that remodel its effector domain

John H. McGee et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Article Oncology

A Convergence-Based Framework for Cancer Drug Resistance

David J. Konieczkowski et al.

CANCER CELL (2018)

Article Biochemistry & Molecular Biology

Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor

Matthew R. Janes et al.

Review Endocrinology & Metabolism

The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway

Mylene Tajan et al.

ENDOCRINE REVIEWS (2018)

Article Biochemistry & Molecular Biology

Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase

Dietrich A. Ruess et al.

NATURE MEDICINE (2018)

Article Biochemistry & Molecular Biology

Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition

Gabrielle S. Wong et al.

NATURE MEDICINE (2018)

Article Biochemistry & Molecular Biology

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

Sara Mainardi et al.

NATURE MEDICINE (2018)

Article Cell Biology

Afatinib restrains K-RAS-driven lung tumorigenesis

Herwig P. Moll et al.

SCIENCE TRANSLATIONAL MEDICINE (2018)

Article Oncology

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

Ferdinandos Skoulidis et al.

CANCER DISCOVERY (2018)

Article Multidisciplinary Sciences

Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib

Elisa Caiola et al.

SCIENTIFIC REPORTS (2018)

Article Medicine, Research & Experimental

Targeting the MAPK Pathway in RAS Mutant Cancers

Sarah G. Hymowitz et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2018)

Review Oncology

Regulatory mechanisms of PD-L1 expression in cancer cells

Yongyu Shi

CANCER IMMUNOLOGY IMMUNOTHERAPY (2018)

Review Cell Biology

The functional diversity of Aurora kinases: a comprehensive review

Estelle Willems et al.

CELL DIVISION (2018)

Review Oncology

Therapeutic strategies to target RAS-mutant cancers

Meagan B. Ryan et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2018)

Article Biochemistry & Molecular Biology

The small GTPases K-Ras, N-Ras, and H-Ras have distinct biochemical properties determined by allosteric effects

Christian W. Johnson et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2017)

Article Multidisciplinary Sciences

Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer

Sushrut Kamerkar et al.

NATURE (2017)

Article Biochemistry & Molecular Biology

Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis

Rodrigo Romero et al.

NATURE MEDICINE (2017)

Article Biochemistry & Molecular Biology

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

Ahmet Zehir et al.

NATURE MEDICINE (2017)

Article Chemistry, Medicinal

Crystal Structure of a Human K-Ras G12D Mutant in Complex with GDP and the Cyclic Inhibitory Peptide KRpep-2d

Satoshi Sogabe et al.

ACS MEDICINAL CHEMISTRY LETTERS (2017)

Review Biochemistry & Molecular Biology

RAS Proteins and Their Regulators in Human Disease

Dhirendra K. Simanshu et al.

Review Hematology

Role of SHP2 in hematopoiesis and leukemogenesis

Ruchi Pandey et al.

CURRENT OPINION IN HEMATOLOGY (2017)

Review Oncology

Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

Zeynep Eroglu et al.

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY (2016)

Editorial Material Oncology

Sticking It to Cancer with Molecular Glue for SHP2

Hao Ran et al.

CANCER CELL (2016)

Review Biochemistry & Molecular Biology

Negative feedback regulation of the ERK1/2 MAPK pathway

David Lake et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2016)

Article Biochemistry & Molecular Biology

Aurora kinase targeting in lung cancer reduces KRAS-induced transformation

Edmilson Ozorio dos Santos et al.

MOLECULAR CANCER (2016)

Review Oncology

Treating cancer with selective CDK4/6 inhibitors

Ben O'Leary et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2016)

Review Biotechnology & Applied Microbiology

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

Jonathan M. L. Ostrem et al.

NATURE REVIEWS DRUG DISCOVERY (2016)

Article Medicine, General & Internal

T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer

Eric Tran et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

Article Multidisciplinary Sciences

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

Piro Lito et al.

SCIENCE (2016)

Review Cell Biology

Functions of Shp2 in cancer

Jie Zhang et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2015)

Article Multidisciplinary Sciences

Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site

Mohammad T. Mazhab-Jafari et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2015)

Review Oncology

MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road

Christopher J. Caunt et al.

NATURE REVIEWS CANCER (2015)

Article Chemistry, Multidisciplinary

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

Sang Min Lim et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2014)

Article Multidisciplinary Sciences

Comprehensive molecular profiling of lung adenocarcinoma

Eric A. Collisson et al.

NATURE (2014)

Article Multidisciplinary Sciences

Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer

Diletta Di Mitri et al.

NATURE (2014)

Article Biochemistry & Molecular Biology

Integrated RAS signaling defined by parallel NMR detection of effectors and regulators

Matthew J. Smith et al.

NATURE CHEMICAL BIOLOGY (2014)

Review Biotechnology & Applied Microbiology

Drugging the undruggable RAS: Mission Possible?

Adrienne D. Cox et al.

NATURE REVIEWS DRUG DISCOVERY (2014)

Article Cell Biology

Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy

Steven L. Highfill et al.

SCIENCE TRANSLATIONAL MEDICINE (2014)

Article Pathology

Intratumoral heterogeneity of KRAS mutation is rare in non-small-cell lung cancer

Winfried H. Alsdorf et al.

EXPERIMENTAL AND MOLECULAR PATHOLOGY (2013)

Article Multidisciplinary Sciences

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

Jonathan M. Ostrem et al.

NATURE (2013)

Review Oncology

The genetics and biology of KRAS in lung cancer

Peter M. K. Westcott et al.

CHINESE JOURNAL OF CANCER (2013)

Review Oncology

A Comprehensive Survey of Ras Mutations in Cancer

Ian A. Prior et al.

CANCER RESEARCH (2012)

Article Biochemistry & Molecular Biology

Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

Marcin Imielinski et al.

Article Biochemistry & Molecular Biology

A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis

Swarnali Acharyya et al.

Article Medicine, Research & Experimental

Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis

Thomas Jamieson et al.

JOURNAL OF CLINICAL INVESTIGATION (2012)

Article Oncology

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

Nathan T. Ihle et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2012)

Article Oncology

WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe

Philip C. De Witt Hamer et al.

CLINICAL CANCER RESEARCH (2011)

Article Gastroenterology & Hepatology

Heterogeneity of KRAS Status May Explain the Subset of Discordant KRAS Status Between Primary and Metastatic Colorectal Cancer

Toshiaki Watanabe et al.

DISEASES OF THE COLON & RECTUM (2011)

Article Cell Biology

Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis

Jessie Yanxiang Guo et al.

GENES & DEVELOPMENT (2011)

Article Medicine, Research & Experimental

Inhibiting Cxcr2 disrupts tumor-stromal interactions and improves survival in a mouse model of pancreatic ductal adenocarcinoma

Hideaki Ijichi et al.

JOURNAL OF CLINICAL INVESTIGATION (2011)

Review Microbiology

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Marie Cargnello et al.

MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS (2011)

Article Medicine, General & Internal

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

Wendy De Roock et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2010)

Article Multidisciplinary Sciences

Somatic mutations affect key pathways in lung adenocarcinoma

Li Ding et al.

NATURE (2008)

Article Biochemistry & Molecular Biology

Recognizing and defining true Ras binding domains 1:: Biochemical analysis

S Wohlgemuth et al.

JOURNAL OF MOLECULAR BIOLOGY (2005)

Review Biochemistry & Molecular Biology

The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling

BG Neel et al.

TRENDS IN BIOCHEMICAL SCIENCES (2003)

Review Biotechnology & Applied Microbiology

Factors that influence the mutagenic patterns of DNA adducts from chemical carcinogens

KY See et al.

MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH (2000)