KRAS Mutations in Non-Small Cell Lung Cancer

Riely, G. J.; Marks, J.; Pao, W.

doi:10.1513/pats.200809-107lc

Cited by 550Lung Cancer Treatments and MutationsProtein Kinase Regulation and GTPase SignalingLung Cancer Diagnosis and Treatment

KRAS Mutations in Non-Small Cell Lung Cancer

Riely, G. J., Marks, J., Pao, W.·2009·Proceedings of the American Thoracic Society

DOI 10.1513/pats.200809-107lc

Open this paper in CoChat — free account

Abstract

Some non-small cell lung cancers (NSCLCs) harbor a single specific mutated oncogene that is thought to be the primary genetic "driver" leading to cancer. The two most commonly mutated oncogenes in lung cancer encode for the epidermal growth factor receptor (EGFR) and KRAS. EGFR kinase domain mutations were only recently identified, but they have already been established in the clinic as valid predictors of increased sensitivity to EGFR kinase inhibitors (gefitinib and erlotinib). By contrast, even though KRAS mutations were identified in NSCLC tumors more than 20 years ago, we have only just begun to appreciate the clinical value of KRAS tumor status. Recent studies indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy, and their disease does not respond to EGFR inhibitors. There is a dire need for therapies specifically for patients with KRAS mutant NSCLC. In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an overview of current approaches to targeting KRAS mutant NSCLC.

Integrity signals

Registry

Crossref · 10.1513/pats.200809-107lc

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

GTP binding to KRAS shifts the active site from an open to a closed conformation, allowing multiple downstream effector pathways including MAPK and PI3K to interact and activate.
“GTP binding to KRAS shifts the active site from an open to a closed conformation, allowing multiple downstream effector pathways to interact and activate, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways [12, 13].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [12]
In patients with lung cancer harboring KRAS mutations, most mutations occur in codon 12, whereas mutations in codons 13 and 61 are less frequent.
“In patients with lung cancer harboring KRAS mutations, the most mutations occur in codon 12, whereas mutations in codons 13 and 61 are less frequent (4).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [4]

ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061 · see citing works
EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib
Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338 · see citing works
Self-citation
Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,262 · see citing works
Epidermal growth factor receptor mutations in lung cancer
Sharma, S. V., Bell, D. W., Settleman, J., & Haber, D. A. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2088 · Cited by 3,170 · see citing works
Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
Pignon, J.-P., Tribodet, H., Scagliotti, G. V., Douillard, J.-Y., Shepherd, F. A., Stephens, R. J., Dunant, A., Torri, V., Rosell, R., Seymour, L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.9030 · Cited by 2,642 · see citing works
KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer
Lièvre, A., Bachet, J.-B., Le Corre, D., Boige, V., Landi, B., Emile, J.-F., Côté, J.-F., Tomasic, G., Penna, C., Ducreux, M., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0191 · Cited by 2,229 · see citing works
Vinorelbine plus Cisplatin vs. Observation in Resected Non–Small-Cell Lung Cancer
Winton, T. L., Livingston, R. B., Johnson, D. H., Rigas, J. R., Johnston, M., Butts, C. A., Cormier, Y. F., Goss, G., Inculet, R., Vallières, E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043623 · Cited by 1,810 · see citing works
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517 · see citing works
Self-citation
KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab
Lièvre, A., Bachet, J., Boige, V., Cayre, A., Corre, D. L., Buc, E., Ychou, M., Bouché, O., Landi, B., Louvet, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.5906 · Cited by 1,456 · see citing works
Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib
Eberhard, D. A., Johnson, B. E., Amler, L. C., Goddard, A. D., Heldens, S., Herbst, R. S., Ince, W. L., Janne, P. A., Januario, T., Johnson, D. H., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.857 · Cited by 1,453 · see citing works
Mechanism of activation of a human oncogene
Tabin, C. J., Bradley, S. M., Bargmann, C. I., Weinberg, R. A., Papageorge, A. G., Scolnick, E. M., Dhar, R., Lowy, D. R., & Chang, E. H. (1982) · Nature · doi:10.1038/300143a0 · Cited by 1,393 · see citing works
A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene
Reddy, E. P., Reynolds, R. K., Santos, E., & Barbacid, M. (1982) · Nature · doi:10.1038/300149a0 · Cited by 1,391 · see citing works
BRAF and RAS mutations in human lung cancer and melanoma.
Brose, M. S., Volpe, P., Feldman, M. D., Kumar, M. S., Rishi, I., Gerrero, R. M., Einhorn, E., Herlyn, M., Minna, J. D., Nicholson, A. G., et al. (2002) · PubMed · Cited by 1,048 · see citing works
Blocking Oncogenic Ras Signaling for Cancer Therapy
Adjei, A. A. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.14.1062 · Cited by 831 · see citing works
Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts
Shih, C., Padhy, L. C., Murray, M. J., & Weinberg, R. A. (1981) · Nature · doi:10.1038/290261a0 · Cited by 791 · see citing works
Understanding Ras: ‘it ain’t over ’til it’s over’
Shields, J. M., Pruitt, K., McFall, A. J., Maddox, A. S., & Der, C. J. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01740-2 · Cited by 780 · see citing works
The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes
Ellis, R. W., DeFeo, D., Shih, T. Y., Gonda, M. A., Young, H. A., Tsuchida, N., Lowy, D. R., & Scolnick, E. M. (1981) · Nature · doi:10.1038/292506a0 · Cited by 723 · see citing works
Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change
Taparowsky, E. J., Suard, Y. M. L., Fasano, O., Shimizu, K., Goldfarb, M. P., & Wigler, M. H. (1982) · Nature · doi:10.1038/300762a0 · Cited by 703 · see citing works
Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer
Hirsch, F. R., Varella-Garcia, M., Bunn, P. A., Franklin, W. A., Dziadziuszko, R., Thatcher, N., Chang, A., Parikh, P., Pereira, J. R., Ciuleanu, T., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.3958 · Cited by 703 · see citing works
Role of KRAS and EGFR As Biomarkers of Response to Erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21
Zhu, C.-Q., da Cunha Santos, G., Ding, K., Sakurada, A., Cutz, J.-C., Liu, N., Zhang, T., Marrano, P., Whitehead, M., Squire, J. A., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.8924 · Cited by 661 · see citing works
Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer
Mitsudomi, T., & Yatabe, Y. (2007) · Cancer Science · doi:10.1111/j.1349-7006.2007.00607.x · Cited by 606 · see citing works
The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis
Mascaux, C., Iannino, N., Martin, B., Paesmans, M., Berghmans, T., Dusart, M., Haller, A., Lothaire, P., Meert, A.-P., Noël, S., et al. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602258 · Cited by 604 · see citing works
KRASMutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Massarelli, E., Varella‐Garcia, M., Tang, X., Xavier, A. C., Ozburn, N. C., Liu, D. D., Bekele, B. N., Herbst, R. S., & Wistuba, I. I. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-3043 · Cited by 594 · see citing works
Increasing Complexity of the Ras Signaling Pathway
Vojtek, A. B., & Der, C. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.19925 · Cited by 580 · see citing works
Frequency and Distinctive Spectrum of KRAS Mutations in Never Smokers with Lung Adenocarcinoma
Riely, G. J., Kris, M. G., Rosenbaum, D., Marks, J., Li, A., Chitale, D. A., Nafa, K., Riedel, E. R., Hsu, M., Pao, W., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0646 · Cited by 578 · see citing works
Self-citation
An Unidentified Virus which causes the Rapid Production of Tumours in Mice
Harvey, J. J. (1964) · Nature · doi:10.1038/2041104b0 · Cited by 554 · see citing works
Detection of p53 Gene Mutations in Human Brain Tumors by Single-strand Conformation Polymorphism Analysis of Polymerase Chain Reaction Products
Mashiyama, S., Kayama, T., Katakura, R., Yoshimoto, T., Murakami, Y., Sekiya, T., & Hayashi, K. (1991) · Springer eBooks · doi:10.1007/978-4-431-68150-2_41 · Cited by 538 · see citing works
Mutational Activation of the K-rasOncogene
Rodenhuis, S., van de Wetering, M. L., Mooi, W. J., Evers, S. G., van Zandwijk, N., & Bos, J. L. (1987) · New England Journal of Medicine · doi:10.1056/nejm198710083171504 · Cited by 532 · see citing works
Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells
Goldfarb, M. P., Shimizu, K., Perucho, M., & Wigler, M. H. (1982) · Nature · doi:10.1038/296404a0 · Cited by 484 · see citing works
Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1
Hall, A., Marshall, C. J., Spurr, N. K., & Weiss, R. A. (1983) · Nature · doi:10.1038/303396a0 · Cited by 438 · see citing works
Malignant Activation of a K- ras Oncogene in Lung Carcinoma But Not in Normal Tissue of the Same Patient
Santos, E., Martin-Zanca, D., Reddy, E. P., Pierotti, M. A., Della Porta, G., & Barbacid, M. (1984) · Science · doi:10.1126/science.6695174 · Cited by 418 · see citing works
Epidermal Growth Factor Receptor Mutations in Non–Small-Cell Lung Cancer: Implications for Treatment and Tumor Biology
Janne, P. A., Engelman, J. A., & Johnson, B. E. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.09.985 · Cited by 405 · see citing works
Three human transforming genes are related to the viral ras oncogenes.
Shimizu, K., Goldfarb, M. P., Suard, Y. M. L., Perucho, M., Li, Y., Kamata, T., Feramisco, J. R., Stavnezer, E., Fogh, J. M., & Wigler, M. H. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.8.2112 · Cited by 389 · see citing works
KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience
Cutsem, E. V., Láng, I., D’Haens, G., Moiseyenko, V. M., Załuski, J., Folprecht, G., Tejpar, S., Kisker, O., Stroh, C., & Rougier, P. R. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.2 · Cited by 372 · see citing works
Direct Demonstration of Geranylgeranylation and Farnesylation of Ki-Ras in Vivo
Rowell, C. A., Kowalczyk, J. J., Lewis, M. D., & Garcia, A. M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14093 · Cited by 368 · see citing works
Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond
Ladanyi, M., & Pao, W. J. (2008) · Modern Pathology · doi:10.1038/modpathol.3801018 · Cited by 365 · see citing works
Self-citation
Prognostic and Predictive Importance of p53 and RAS for Adjuvant Chemotherapy in Non–Small-Cell Lung Cancer
Tsao, M., Aviel‐Ronen, S., Ding, K., Lau, D., Liu, G., Sakurada, A., Whitehead, M., Zhu, C., Livingston, R. B., Johnson, D. H., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.6953 · Cited by 326 · see citing works
Morphologic Responses to a Murine Erythroblastosis Virus 2
KIRSTEN, W. H., & Mayer, L. A. (1967) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/39.2.311 · Cited by 306 · see citing works
Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer
Jackman, D. M., Yeap, B. Y., Lindeman, N. I., Fidias, P., Rabin, M. S., Temel, J. S., Skarin, A. T., Meyerson, M. M., Tisch, A. H., Borras, A. M., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.5754 · Cited by 304 · see citing works
Biomarkers of Response to Epidermal Growth Factor Receptor Inhibitors in Non–Small-Cell Lung Cancer Working Group: Standardization for Use in the Clinical Trial Setting
Eberhard, D. A., Giaccone, G., & Johnson, B. E. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.9858 · Cited by 300 · see citing works
Molecular Characteristics of Bronchioloalveolar Carcinoma and Adenocarcinoma, Bronchioloalveolar Carcinoma Subtype, Predict Response to Erlotinib
Miller, V. A., Riely, G. J., Zakowski, M. F., Li, A. R., Patel, J. D., Heelan, R. T., Kris, M. G., Sandler, A. B., Carbone, D. P., Tsao, A. S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.13.0062 · Cited by 295 · see citing works
Self-citation
Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: Lessons from mechanism and bench-to-bedside translational studies
Sebti, S. M., & Hamilton, A. D. (2000) · Oncogene · doi:10.1038/sj.onc.1204146 · Cited by 278 · see citing works
Prognostic and Therapeutic Implications of EGFR and KRAS Mutations in Resected Lung Adenocarcinoma
Marks, J. L., Broderick, S., Zhou, Q. C., Chitale, D. A., Li, A. R., Zakowski, M. F., Kris, M. G., Rusch, V. W., Azzoli, C. G., Seshan, V., et al. (2008) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318160c607 · Cited by 268 · see citing works
Self-citation
Oncogenes in human tumor cell lines: molecular cloning of a transforming gene from human bladder carcinoma cells.
Pulciani, S., Santos, E., Lauver, A. V., Long, L. K., Robbins, K. C., & Barbacid, M. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.9.2845 · Cited by 268 · see citing works
Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib
Hirsch, F. R., Varella‐Garcia, M., Cappuzzo, F., McCoy, J., Bemis, L., Xavier, A. C., Dziadziuszko, R., Gumerlock, P. H., Chansky, K., West, H., et al. (2007) · Annals of Oncology · doi:10.1093/annonc/mdm003 · Cited by 266 · see citing works
Optimization of Patient Selection for Gefitinib in Non–Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation
Han, S., Kim, T., Jeon, Y. K., Hwang, P. G., Im, S., Lee, K.-H., Kim, J. H., Kim, D., Heo, D. S., Kim, N. K., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2845 · Cited by 250 · see citing works
KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience
Bokemeyer, C., Bondarenko, I., Hartmann, J. T., de Braud, F., Volovat, C. D., Nippgen, J., Stroh, C., Celik, I., & Koralewski, P. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.4000 · Cited by 240 · see citing works
Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas
Ceppa, D. P., Kris, M. G., Riely, G. J., Sarkaria, I. S., McDonough, T. L., Chuai, S., Venkatraman, E. S., Miller, V. A., Ladanyi, M., Pao, W. J., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.3224 · Cited by 210 · see citing works
Self-citation
Lack of Prognostic Significance of p53 and K-ras Mutations in Primary Resected Non–Small-Cell Lung Cancer on E4592: A Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy
Schiller, J. H., Adak, S., Feins, R. H., Keller, S. M., Fry, W. A., Livingston, R. B., Hammond, M. E., Wolf, B. C., Sabatini, L. M., Jett, J. R., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.2.448 · Cited by 192 · see citing works
EGFR Tyrosine Kinase Inhibitors in Lung Cancer: An Evolving Story
Sequist, L. V. D., & Lynch, T. J. (2007) · Annual Review of Medicine · doi:10.1146/annurev.med.59.090506.202405 · Cited by 156 · see citing works
EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer
van Zandwijk, N., Mathy, A., Boerrigter, L., Ruijter, H. J., Tielen, I. H. G., de Jong, D., Baas, P., Burgers, S. A., & Nederlof, P. M. (2006) · Annals of Oncology · doi:10.1093/annonc/mdl323 · Cited by 146 · see citing works
High Expression of ErbB Family Members and Their Ligands in Lung Adenocarcinomas That Are Sensitive to Inhibition of Epidermal Growth Factor Receptor
Fujimoto, N., Wislez, M., Zhang, J., Iwanaga, K., Dackor, J., Hanna, A. E., Kalyankrishna, S., CODY, D. D., Price, R. E., Sato, M., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1977 · Cited by 146 · see citing works
RAS inhibitors: potential for cancer therapeutics
Kloog, Y., & Cox, A. D. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(00)01789-5 · Cited by 85 · see citing works
A Phase II Pharmacodynamic Study of Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy
Felip, E., Rojo, F., Reck, M., Heller, A., Klughammer, B., Sala, G., Cedrés, S., Peralta, S., Maacke, H., Foernzler, D., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5186 · Cited by 78 · see citing works
New exchange, new target
Downward, J. (1998) · Nature · doi:10.1038/24743 · Cited by 42 · see citing works

Flagged first, then by citations

Sorted by citations

Non-small cell lung cancer: current treatment and future advances
Zappa, C., & Mousa, S. A. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.06.07 · Cited by 1,944 · see citing works
American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer
Azzoli, C. G., Baker, S., Temin, S., Pao, W., Aliff, T., Brahmer, J., Johnson, D. H., Laskin, J. L., Masters, G., Milton, D., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.5622 · Cited by 915 · see citing works
Self-citation
Cell death-based treatment of lung adenocarcinoma
Denisenko, T. V., Budkevich, I. N., & Zhivotovsky, B. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0063-y · Cited by 768 · see citing works
Targeting Lactate Dehydrogenase-A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells
Xie, H., Hanai, J.-I., Ren, J.-G., Kats, L., Burgess, K., Bhargava, P., Signoretti, S., Billiard, J., Duffy, K. J., Grant, A., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.003 · Cited by 516 · see citing works
Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice
Sequist, L. V., Heist, R. S., Shaw, A. T., Fidias, P., Rosovsky, R., Temel, J. S., Lennes, I. T., Digumarthy, S., Waltman, B. A., Bast, E., et al. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr489 · Cited by 370 · see citing works
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)
Blumenschein, G. R., Smit, E. F., Planchard, D., Kim, D.-W., Cadranel, J., De Pas, T., Dunphy, F., Udud, K., Ahn, M.-J., Hanna, N. H., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv072 · Cited by 349 · see citing works
Broad, Hybrid Capture–Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches
Drilon, A., Wang, L., Arcila, M. E., Balasubramanian, S., Greenbowe, J. R., Ross, J. S., Stephens, P., Lipson, D., Miller, V. A., Kris, M. G., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2683 · Cited by 274 · see citing works
Targeting KRAS mutant cancers: from druggable therapy to drug resistance
Zhu, C., Guan, X., Zhang, X., Luan, X., Song, Z., Cheng, X., Zhang, W., & Qin, J.-J. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01629-2 · Cited by 231 · see citing works
Prognostic and Predictive Value inKRASin Non–Small-Cell Lung Cancer: A Review
Wood, K., Hensing, T., Malik, R., & Salgia, R. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.0405 · Cited by 164 · see citing works
Predictive radiogenomics modeling of EGFR mutation status in lung cancer
Gevaert, O., Echegaray, S., Khuong, A., Hoang, C. D., Shrager, J. B., Jensen, K. C., Berry, G. J., Guo, H. H., Lau, C., Plevritis, S. K., et al. (2017) · Scientific Reports · doi:10.1038/srep41674 · Cited by 160 · see citing works
Loss of PTEN expression by blocking nuclear translocation of EGR1 in gefitinib-resistant lung cancer cells harboring epidermal growth factor receptor-activating mutations
Yamamoto, C., Basaki, Y., Kawahara, A., Nakashima, K., Kage, M., Izumi, H., Kohno, K., Uramoto, H., Yasumoto, K., Kuwano, M., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0043 · Cited by 155 · see citing works
Mechanisms of Resistance to KRASG12C-Targeted Therapy
Akhave, N. S., Biter, A. B., & Hong, D. S. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1616 · Cited by 156 · see citing works
Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer
Tong, X., Patel, A. S., Kim, E., Li, H., Chen, Y., Li, S., Liu, S., Dilly, J., Kapner, K. S., Zhang, N., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.01.012 · Cited by 142 · see citing works
New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness
Yang, H., Liang, S.-Q., Schmid, R. A., & Peng, R.-W. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00953 · Cited by 129 · see citing works
KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma
Rekhtman, N., Ang, D. C., Riely, G. J., Ladanyi, M., & Moreira, A. L. (2013) · Modern Pathology · doi:10.1038/modpathol.2013.74 · Cited by 117 · see citing works
Self-citation
A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer
Vasan, N., Boyer, J. L., & Herbst, R. S. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1762 · Cited by 102 · see citing works
KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy
Guan, J.-L., Zhong, W.-Z., An, S.-J., Yang, J.-J., Su, J., Chen, Z.-H., Yan, H.-H., Chen, Z.-Y., Huang, Z.-M., Zhang, X.-C., et al. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2754-z · Cited by 87 · see citing works
Pulsatile MEK inhibition improves anti-tumor immunity and T cell function in murine Kras mutant lung cancer
Choi, H., Deng, J., Li, S., Silk, T., Dong, L., Brea, E. J., Houghton, S., Redmond, D., Zhong, H., Boiarsky, J., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.066 · Cited by 72 · see citing works
KRAS Mutation Status Is Associated with Enhanced Dependency on Folate Metabolism Pathways in Non–Small Cell Lung Cancer Cells
Moran, D. M., Trusk, P. B., Pry, K., Paz, K., Sidransky, D., & Bacus, S. S. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0649 · Cited by 64 · see citing works
Targeted Degradation of KRAS by an Engineered Ubiquitin Ligase Suppresses Pancreatic Cancer Cell Growth In Vitro and In Vivo
Ma, Y., Gu, Y., Zhang, Q., Han, Y., Yu, S., Lu, Z., & Chen, J. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0650 · Cited by 55 · see citing works
Distinct dynamics and interaction patterns in H- and K-Ras oncogenic P-loop mutants: Interaction Patterns in Ras Oncogenic Mutants
Sayyed-Ahmad, A., Prakash, P., & Gorfe, A. A. (2017) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25317 · Cited by 54 · see citing works
The role of wild-type RAS in oncogenic RAS transformation
Sheffels, E., & Kortum, R. L. (2021) · Genes · doi:10.3390/genes12050662 · Cited by 42 · see citing works
“KRAS is the most frequently mutated RAS family member (75% of RAS mutations), including high incidence of mutations in lung [4], colon [5], and pancreatic cancers [6], three of the top four causes of cancer-related death [2,7,8].”
Background
Single Copies of Mutant KRAS and Mutant PIK3CA Cooperate in Immortalized Human Epithelial Cells to Induce Tumor Formation
Wang, G. M., Wong, H. Y., Konishi, H., Blair, B. G., Abukhdeir, A. M., Gustin, J. P., Rosen, D. M., Denmeade, S. R., Rasheed, Z., Matsui, W., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-1578 · Cited by 39 · see citing works
SRC and MEK Co-inhibition Synergistically Enhances the Anti-tumor Effect in Both Non-small-cell Lung Cancer (NSCLC) and Erlotinib-Resistant NSCLC
Yuan, M., Xu, L.-F., Zhang, J., Kong, S.-Y., Wu, M., Lao, Y.-Z., Zhou, H., Zhang, L., & Xu, H. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00586 · Cited by 26 · see citing works
scGraph2Vec: a deep generative model for gene embedding augmented by graph neural network and single-cell omics data
Lin, S., & Jia, P. (2024) · GigaScience · doi:10.1093/gigascience/giae108 · Cited by 4 · see citing works

Comparison of the therapeutic outcome between gefitinib and erlotinib in female patients with non-small-cell lung cancer
문대성, 장태원, Ok, C. H., 정만홍, 김도현, & 최인수 (2009) · The Korean Journal of Internal Medicine
Gefitinib or erlotinib in the treatment of advanced non-small cell lung cancer.
Shao, Y., Lin, C., & Yang, C.-H. (2010) · PubMed · Cited by 13 · see citing works
Successful Treatment of Non-small Cell Lung Cancer with Gefitinib after Severe Erlotinib-related Hepatotoxicity
Kunimasa, K., Yoshioka, H., Iwasaku, M., et al. (2012) · Internal Medicine · doi:10.2169/internalmedicine.51.6285 · Cited by 26 · see citing works
Erlotinib as a salvage treatment for patients with advanced non-small cell lung cancer after failure of gefitinib treatment
Сонг, Zheng-bo, Yu, et al. (2011) · 中华医学杂志：英文版
Erlotinib is a well-tolerated alternate treatment for non-small cell lung cancer in cases of gefitinib-induced hepatotoxicity.
Yonesaka, K., Suzumura, T., Tsukuda, H., Hasegawa, Y., Ozaki, T., Sugiura, T., & Fukuoka, M. (2014) · PubMed · Cited by 13 · see citing works

Authors: Riely, G. J., Marks, J., & Pao, W.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
ORCID: Riely, G. J.
Pao, W.
Venue: Proceedings of the American Thoracic Society
Publisher: Oxford University Press (OUP)
Published: 2009-04-15
Volume: 6
Issue: 2
Pages: 201-205
ISSN: 1546-3222 (ISSN-L)
DOI: 10.1513/pats.200809-107lc
OpenAlex: W2029446677
Cited by: 550
References: 55
Citations by year: 2026: 4 · 2025: 12 · 2024: 23 · 2023: 21 · 2022: 26 · 2021: 25 · 2020: 24 · 2019: 27 · 2018: 29 · 2017: 33 · 2016: 34 · 2015: 39 · 2014: 53 · 2013: 57 · 2012: 57
FWCI: 39.86
Type: journal article
Language: en
Open access: closed
Locations: Proceedings of the American Thoracic Society (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords: KRAS mutation, non-small cell lung cancer, oncogenic Ras, EGFR mutation, EGFR kinase inhibitors, gefitinib, erlotinib, adjuvant chemotherapy, predictive biomarkers, targeted therapy, clinical outcomes
MeSH terms: Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Proto-Oncogene Proteins, Risk Factors, Proto-Oncogene Proteins p21(ras), ras Proteins, ErbB Receptors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

KRAS Mutations in Non-Small Cell Lung Cancer

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks