Cited by 1,902Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesMelanoma and MAPK Pathways

The DOI matches its Crossref record; 122 of the 122 references it cites were found in a registry or an index.

RAS oncogenes: the first 30 years

Malumbres, Marcos, Barbacid, Mariano·2003·Nature Reviews Cancer

Open this paper in CoChat — free account

Abstract

From the pioneering work with acute transforming retroviruses to the current post-genomic era, RAS genes have always been at the leading edge of signal transduction and molecular oncology. Yet, a complete understanding of RAS function and dysfunction - mainly in human cancer - is still to come. The knowledge that has accumulated since their discovery 30 years ago has, however, been remarkable, and should pave the way for not only solving the outstanding issues regarding RAS biology, but also for developing efficacious drugs that could have a significant impact on cancer treatment.

Integrity signals

Registry

Crossref · 10.1038/nrc1097

Cites

122 of 122 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?

1 retracted

The Human c- ras 1 H Oncogene: a Mutation in Normal and Neoplastic Tissue from the Same Patient
Muschel, R. J., Khoury, G., Lebowitz, P., Koller, R. P., & Dhar, R. (1983) · Science · doi:10.1126/science.6337398 · Cited by 18
Retracted
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
TGF-β SIGNAL TRANSDUCTION
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061
Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,354
Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes
Land, H., Parada, L. F., & Weinberg, R. A. (1983) · Nature · doi:10.1038/304596a0 · Cited by 2,804
Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
Almoguera, C., Shibata, D. K., Forrester, K., Wj, M., Arnheim, N., & Perucho, M. (1988) · Cell · doi:10.1016/0092-8674(88)90571-5 · Cited by 2,122
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954
Mammalian Ras interacts directly with the serine/threonine kinase raf
Vojtek, A. B., Hollenberg, S. M., & Cooper, J. A. (1993) · Cell · doi:10.1016/0092-8674(93)90307-c · Cited by 1,934
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-rasPreprint
Jackson, E. L., Willis, N. A., Mercer, K. L., Bronson, R. T., Crowley, D. G., Montoya, R., Jacks, T., & Tuveson, D. A. (2001) · Genes & Development · doi:10.1101/gad.943001 · Cited by 1,927

Flagged first, then by citations

Show all 122 references

Sorted by citations

Items 901–1,000 of 1,002

N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation
Wu, M. H., Huang, J., Zhang, J., Benes, C. H., Jiao, B., & Ren, R. (2016) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0419 · Cited by 20
“Mol Cancer Ther; 16(1) January 2017 Molecular Cancer Therapeutics 64”
BackgroundInfluential
Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients
Scrima, M., Marino, F. Z., Oliveira, D. M., Marinaro, C., Mantia, E. L., Rocco, G., Marco, C. D., Malanga, D., Rosa, N. D., Rizzuto, A., et al. (2017) · Journal of Cancer · doi:10.7150/jca.17093 · Cited by 20
“Once dysregulated, these cascades play a major role in cancer development [4, 28-32].”
Background
The role of the NORE1A tumor suppressor in Oncogene-Induced Senescence
Barnoud, T., Schmidt, M., Donninger, H., & Clark, G. J. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.04.030 · Cited by 20
Cancer as an ecomolecular disease and a neoplastic consortium
y Cajal, S. R., Capdevila, C., Hernández‐Losa, J., Mattos‐Arruda, L. D., Ghosh, A., Lorent, J., Larsson, O. S., Aasen, T., Postovit, L.-M. M., & Topisirović, I. (2017) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2017.09.004 · Cited by 20
“For instance, no effective therapies have been found for KRAS mutation-driven tumors, even though >20% of all cancers harbor mutations in this gene and its aberrant activation is associated with resistance to anti-epidermal growth factor receptor (EGFR) therapies and other anticancer agents (29).”
Background
An update on the use of Raman spectroscopy in molecular cancer diagnostics: current challenges and further prospects
Upchurch, E., Isabelle, M., Lloyd, G. R., Kendall, C. A., & Barr, H. (2018) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2018.1439739 · Cited by 20
“There are, however, different mutations in this gene which result in different oncogenic properties [9].”
Background
Targeted Therapies in Veterinary Oncology
Londhe, P., Gutwillig, M., & London, C. A. (2019) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2019.04.005 · Cited by 20
Rap1a deficiency modifies cytokine responses and MAPK-signaling in vitro and impairs the in vivo inflammatory response
Dorn, A., Zoellner, A., Follo, M., Martin, S. F., Weber, F. C., Marks, R., Melchinger, W., Zeiser, R., Fisch, P., & Scheele, J. S. (2012) · Cellular Immunology · doi:10.1016/j.cellimm.2012.05.008 · Cited by 20
The relative influence of diet and serum concentrations of organochlorine compounds on K-ras mutations in exocrine pancreatic cancer
Gasull, M., Porta, M. S., Pumarega, J. A., Vioqué, J., de Basea, M. B., Puigdomènech, E., Morales, E., Grimalt, J. O., & Malats, N. (2010) · Chemosphere · doi:10.1016/j.chemosphere.2010.03.011 · Cited by 20
“Wild-type EPC and K-ras mutated EPC may develop through pathways involving different host-gene-environment interactions (Crous-Bou, 2009; Bautista et al., 1997; Porta et al., 1999, 2009b,d; Hoppin et al., 2000; Ekbom and Hunter, 2002; Malumbres and Barbacid, 2003; Li et al., 2005; Soliman et al., 2006; Morales et al.,…”
Background
Clinicopathology and Genetic Profile of Synchronous Multiple Small Adenocarcinomas: Implication for Surgical Treatment of an Uncommon Lung Malignancy
Lin, M., Wu, C., Kuo, S., Chang, Y., & Yang, P. (2014) · Annals of Surgical Oncology · doi:10.1245/s10434-014-3642-5 · Cited by 20
Immortalized cells as experimental models to study cancer
Boehm, J. S., & Hahn, W. C. (2004) · Cytotechnology · doi:10.1007/s10616-004-5125-1 · Cited by 22
RNA Aptamers Targeting the Carboxyl Terminus of KRAS Oncoprotein Generated by an Improved SELEX with Isothermal RNA Amplification
Tanaka, Y., Akagi, K., Nakamura, Y., & Kozu, T. (2007) · Oligonucleotides · doi:10.1089/oli.2006.0035r1 · Cited by 20
“T HE RAS PROTEIN is a key molecular switch that signals cell proliferation, division, and mortality (Downward, 2003; Malumbres and Barbacid, 2003).”
The pancreatic cancer proteome – recent advances and future promise
Aspinall-O’Dea, M., & Costello, E. (2007) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200700144 · Cited by 20
Biomarker-driven and molecular targeted therapies for colorectal cancers
Schirripa, M., Cohen, S. A., Battaglin, F., & Lenz, H. (2017) · Seminars in Oncology · doi:10.1053/j.seminoncol.2017.06.003 · Cited by 25
“KRAS is a small GTPase protein member of the RAS family [9,10], and its constitutive activation, gained through somatic gene mutations, results in cell proliferation and survival independent of external cellular signals [11].”
Background
Design, in silico modeling, biodistribution study of rutin and quercetin loaded stable human hair keratin nanoparticles intended for anticancer drug delivery
Kunjiappan, S., Panneerselvam, T., Somasundaram, B., Murugesan, S., Chowdhury, R., Chowdhury, A., & Bhattacharjee, C. (2017) · Biomedical Physics & Engineering Express · doi:10.1088/2057-1976/aaa1cf · Cited by 20
Oncogenes and Tumor Angiogenesis
Rak, J. W., & Kerbel, R. S. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-313-2_10 · Cited by 20
Synergistic effects of eIF4A and MEK inhibitors on proliferation of NRAS-mutant melanoma cell lines
Malka-Mahieu, H., Girault, I., Rubington, M., Leriche, M., Welsch, C., Kamsukom, N., Zhao, Q., Désaubry, L., Vagner, S., & Robert, C. (2016) · Cell Cycle · doi:10.1080/15384101.2016.1208862 · Cited by 14
“Activating mutations of the NRAS (neuroblastoma rat sarcoma viral oncogene) protein kinase inducing a constitutive activation of the MAPK and PI3K/Akt/mTOR pathways(1) are present in 15– 20% of melanomas and in a plethora of other cancers types such as leukemia, lung cancers and colorectal cancers.(2,3) The NRAS Q61 m…”
Background
Dynamic Multilevel Regulation of EGFR, KRAS, and MYC Oncogenes: Driving Cancer Cell Proliferation Through (Epi)Genetic and Post-Transcriptional/Translational Pathways
Šereš, M., Spacayova, K., Sulová, Z., Špaldová, J., Breier, A., & Pavlíková, L. (2025) · Cancers · doi:10.3390/cancers17020248 · Cited by 28
Decoding RAS isoform and codon-specific signalling
Newlaczyl, A. U., Hood, F. E., Coulson, J. M., & Prior, I. A. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140057 · Cited by 20
Targeting KRAS-mutant non-small cell lung cancer: challenges and opportunities
Zhang, J., Park, D., Shin, D. M., & Deng, X. (2015) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmv118 · Cited by 20
KRAS4A induces metastatic lung adenocarcinomas in vivo in the absence of the KRAS4B isoform
Salmón, M., Paniagua, G., Lechuga, C. G., Fernández-García, F., Zarzuela, E., Álvarez, R., Musteanu, M., Guerra, C. E., Caleiras, E. J., Muñoz, J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023112118 · Cited by 19
Self-citation
New Approaches with Precision Medicine in Adult Brain Tumors
Leibetseder, A., Preusser, M., & Berghoff, A. S. (2022) · Cancers · doi:10.3390/cancers14030712 · Cited by 19
“Tu ors’ resistance against RAF inhibitor monotherapy frequently occurs ue to m i - te ance of MAPK pathway activation [72] and prompted the recommendati n of ad ing a MEK inhibitor in order to set another blockade.”
Background
Kinase dysfunction and kinase inhibitors
London, C. A. (2013) · Veterinary Dermatology · doi:10.1111/j.1365-3164.2012.01081.x · Cited by 19
Gene therapy of pancreatic cancer targeting the K-Ras oncogene
Lisiansky, V., Naumov, I., Shapira, S., Kazanov, D., Starr, A., Arber, N., & Kraus, S. R. (2012) · Cancer Gene Therapy · doi:10.1038/cgt.2012.73 · Cited by 19
Wnt4 inhibits cell motility induced by oncogenic Ras
Menna, M. D., D'Amato, V., Ferraro, A., Fusco, A., Lauro, R. D., Garbi, C., & Vita, G. D. (2012) · Oncogene · doi:10.1038/onc.2012.419 · Cited by 19
MicroRNAs in Bladder Cancer: Expression Profiles, Biological Functions, Regulation, and Clinical Implications
Shi, Z., Wei, Q., Zhang, M., & She, J. (2014) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukaryotgeneexpr.2014007798 · Cited by 19
Binding properties and biological characterization of new sugar-derived Ras ligands
Sacco, E., Abraham, S. J., Palmioli, A., Damore, G., Bargna, A., Mazzoleni, E., Gaponenko, V., Vanoni, M., & Peri, F. (2011) · MedChemComm · doi:10.1039/c0md00264j · Cited by 19
Activation of Ras-Ral Pathway Attenuates p53-independent DNA Damage G2 Checkpoint
Agapova, L. S., Volodina, Y. L., Chumakov, P. M., & Kopnin, B. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405007200 · Cited by 19
BAY61-3606 Affects the Viability of Colon Cancer Cells in a Genotype-Directed Manner
Lau, K. S., Zhang, T., Kendall, K., Lauffenburger, D. A., Gray, N. S., & Haigis, K. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041343 · Cited by 19
“RAS family GTPases act as binary switches that undergo a conformational change upon binding to GTP, allowing them to engage a host of downstream signaling effectors including RAF, PI3K, and RALGDS [1].”
Background
Genetics of Bladder Malignant Tumors in Childhood
Zangari, A., Zaini, J., & Gulìa, C. (2015) · Current Genomics · doi:10.2174/1389202916666151014221954 · Cited by 19
“The role for wild-type Pax3 and Pax7 in neurogenesis during early development is well-established [29].”
Background
SP174 Antibody Lacks Specificity for NRAS Q61R and Cross-Reacts With HRAS and KRAS Q61R Mutant Proteins in Malignant Melanoma
Felisiak-Gołąbek, A., Inaguma, S., Kowalik, A., Wasąg, B., Wang, Z.-F., Zięba, S., Pięciak, L., Ryś, J., Kopczyński, J., Sarlomo‐Rikala, M., et al. (2017) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000500 · Cited by 19
Inducible Intestine-Specific Expression of kras Triggers Intestinal Tumorigenesis In Transgenic Zebrafish
Lu, J., Raghuram, D., Fong, P.-S. A., & Gong, Z. (2018) · Neoplasia · doi:10.1016/j.neo.2018.10.002 · Cited by 20
Inference of Cancer-specific Gene Regulatory Networks Using Soft Computing Rules
Wang, X., & Gotoh, O. (2010) · Gene Regulation and Systems Biology · doi:10.4137/grsb.s4509 · Cited by 19
“DES 0 2 (2) 4 (3) 15 (10) 33 (25) 11 (8) MYL9 0 0 7 (6) 22 (17) 40 (33) 14 (11) CSRP1 1 (1) 3 (2) 3 (2) 9 (5) 18 (13) 7 (5) ACTA2 0 0 11 (10) 28 (22) 30 (22) 14 (11) SPARCL1 1 (1) 2 (2) 6 (5) 20 (13) 36 (28) 13 (10) KCNMB1 0 0 13 (10) 24 (15) 40 (29) 15 (9) Mgp 0 0 12 (8) 30 (21) 47 (36) 18 (13) SLC2A4 0 0 10 (9) 27 (…”
RTK/ERK Pathway under Natural Selection Associated with Prostate Cancer
Chen, Y., Xin, X., Li, J., Xu, J., Yu, X., Li, T., Mo, Z., & Hu, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078254 · Cited by 19
Peroxisome Proliferator-Activated Receptor β/δ Cross Talks with E2F and Attenuates Mitosis in HRAS-Expressing Cells
Zhu, B., Khozoie, C., Bility, M. T., Ferry, C. H., Blazanin, N., Glick, A. B., Gonzalez, F. J., & Peters, J. M. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00092-12 · Cited by 19
“Neoplastic conversion of normal cells to benign tumors and progression of benign tumors to adenomas and carcinomas is associated with overexpression, amplification, and homozygosity of oncogenic Hras (37).”
Background
Involvement of oncogenic K-ras on cell migration stimulated by lysophosphatidic acid receptor-2 in pancreatic cancer cells
Yoshikawa, K., Tanabe, E., Shibata, A., Inoue, S., Kitayoshi, M., Okimoto, S., Fukushima, N., & Tsujiuchi, T. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.09.014 · Cited by 19
An increase in integrin-linked kinase non-canonically confers NF-κB-mediated growth advantages to gastric cancer cells by activating ERK1/2
Tseng, P., Chen, C., Shan, Y., Chang, W., Liu, H., Hong, T.-M., Hsieh, C.-Y., Lin, S., & Lin, C. (2014) · Cell Communication and Signaling · doi:10.1186/s12964-014-0069-3 · Cited by 19
“Ras is a small GTPase that can hydrolyze GTP into GDP in a GTP-bound protein to inactivate the protein, a process accelerated by GAPs, and this process can be reversed with a guanine nucleotide exchange factor to reactivate the Raf/MAPK pathway [27].”
BackgroundInfluential
Ras Family Small GTPase-Mediated Neuroprotective Signaling in Stroke
Shi, G., Andres, D., & Cai, W. (2011) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152411796011349 · Cited by 19
“Ras family GTPases comprise a large group of small molecular weight GTP-binding proteins that share a high degree of amino acid conservation within the five Ras core regions (the G1-G5 domains) which are essential for GTP binding and hydrolysis [26].”
BackgroundInfluential
Development of a Nucleotide Exchange Inhibitor That Impairs Ras Oncogenic Signaling
Marín‐Ramos, N. I., Piñar, C., Vázquez‐Villa, H., Martín‐Fontecha, M., González, Á., Canales, Á., Algar, S., Mayo, P. P., Jiménez‐Barbero, J., Gajate, C., et al. (2016) · Chemistry - A European Journal · doi:10.1002/chem.201604905 · Cited by 19
Targeting Ras signaling in AML: RALB is a small GTPase with big potential
Pomeroy, E. J., & Eckfeldt, C. E. (2017) · Small GTPases · doi:10.1080/21541248.2017.1339765 · Cited by 19
“1).(7) The mitogen-activated protein kinase (MAPK) and”
Increased Incidence of Squamous Cell Carcinomas in Mastomys natalensis Papillomavirus E6 Transgenic Mice during Two-Stage Skin Carcinogenesis
Helfrich, I., Chen, M., Schmidt, R., Fürstenberger, G., Kopp‐Schneider, A., Trick, D., Gröne, H., Hausen, H. Z., & Rösl, F. (2004) · Journal of Virology · doi:10.1128/jvi.78.9.4797-4805.2004 · Cited by 19
“The ras family oncogenes have been detected with high frequency in both human (26) and animal (4, 31) cancers.”
Background
Src Cooperates with Oncogenic Ras in Tumourigenesis via the JNK and PI3K Pathways in Drosophila epithelial Tissue
Poon, C. L. C., Brumby, A. M., & Richardson, H. E. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061585 · Cited by 19
Autophagy buffers Ras-induced genotoxic stress enabling malignant transformation in keratinocytes primed by human papillomavirus
Lopes, E. C., Dias, M. H., da Silva, M. S., Zeidler, J. D., Vessoni, A. T., Reis, M. S., Boccardo, E., & Armelin, H. A. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03476-3 · Cited by 16
Characterization of the Second Ion-Binding Site in the G Domain of H-Ras
O’Connor, C., & Kovrigin, E. L. (2012) · Biochemistry · doi:10.1021/bi301304g · Cited by 18
Mutation Analysis of Braf Exon 15 and Kras Codons 12 and 13 in Moroccan Patients with Colorectal Cancer
Bennani, B., Gilles, S., Fina, F., Nanni, I., Ibrahimi, S. A., Riffi, A. A., Nejjari, C., Benajeh, D.-A., Abkari, M. E., Martin, P., et al. (2010) · The International Journal of Biological Markers · doi:10.5301/jbm.2010.6091 · Cited by 18
“RAS proteins are essential in controlling the activity of several crucial signaling pathways (1-3).”
Background
Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: Part I
Yang, J. S., Song, D., Lee, B., Ko, W. J., Park, S.-K., Won, M., Lee, K., Kim, H. M., & Han, G. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.04.009 · Cited by 18
A mouse model to identify cooperating signaling pathways in cancer
Musteanu, M., Blaas, L., Zenz, R., Svinka, J., Hoffmann, T., Grabner, B., Schramek, D., Kantner, H.-P., Müller, M. M., Kolbe, T., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2130 · Cited by 18
Temporally-regulated quick activation and inactivation of Ras is important for olfactory behaviour
Uozumi, T., Hirotsu, T., Yoshida, K., Yamada, R., Suzuki, A., Taniguchi, G., Iino, Y., & Ishihara, T. (2012) · Scientific Reports · doi:10.1038/srep00500 · Cited by 18
Second-Line Palliative Chemotherapy in Advanced Gall Bladder Cancer, CAP-IRI: Safe and Effective Option
Ramaswamy, A., Ostwal, V. S., Pande, N., Sahu, A., Jandyal, S., Ramadwar, M. R., Shetty, N., Patkar, S., Goel, M., & Gupta, S. (2016) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-016-9828-2 · Cited by 18
Pyrazole-based potent inhibitors of GGT1: Synthesis, biological evaluation, and molecular docking studies
Mansha, M., Udayappan, U. K., Cournia, Z., & Ullah, N. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.09.002 · Cited by 18
Human platelet lysate versus minoxidil stimulates hair growth by activating anagen promoting signaling pathways
Dastan, M., Najafzadeh, N., Abedelahi, A., Sarvi, M., & Niapour, A. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.10.019 · Cited by 21
KRAS mutation in secondary malignant histiocytosis arising from low grade follicular lymphoma
Choi, S. M., Andea, A. A., Wang, M., Behdad, A., Shao, L., Zhang, Y., Lu, X., Dittmann, D., Castro, J., Chen, Y.-H., et al. (2018) · Diagnostic Pathology · doi:10.1186/s13000-018-0758-0 · Cited by 20
Amphiphile-Mediated Depalmitoylation of Proteins in Living Cells
Rudd, A. K., Brea, R. J., & Devaraj, N. K. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b10806 · Cited by 18
Oncogenic K-Ras4B Dimerization Enhances Downstream Mitogen-activated Protein Kinase Signaling
Muratcioğlu, S., Aydın, C., Odabasi, E., Özdemir, E. S., Firat‐Karalar, E. N., Jang, H., Tsai, C., Nussinov, R., Kavaklı, İ. H., Gürsoy, A., et al. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.002 · Cited by 19
“Among the three isoforms, KRAS is the most frequently mutated gene in the Ras family [12] and is involved in more than 91% of pancreatic, 42% of colorectal, and 33% of lung cancers [13].”
Background
Pleiotropic Roles of Calmodulin in the Regulation of KRas and Rac1 GTPases: Functional Diversity in Health and Disease
Tebar, F., Chavero, A., Agell, N., Lu, A., Rentero, C., Enrich, C., & Grewal, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103680 · Cited by 21
Targeting the GCK pathway: a novel and selective therapeutic strategy against RAS-mutated multiple myeloma
Li, S., Fu, J., Yang, J., Ma, H., Bhutani, D., Mapara, M. Y., Marcireau, C., & Lentzsch, S. (2020) · Blood · doi:10.1182/blood.2020006334 · Cited by 18
Regulation of homeostasis and oncogenesis in the intestinal epithelium by Ras
Velho, S., & Haigis, K. M. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.06.002 · Cited by 18
“Oncogenic missense mutations at codons 12, 13, 61, and 146 strongly attenuate GTPase activity and cause RAS to accumulate in the active GTPbound state, resulting in sustained activation of downstream signaling pathways [3].”
Background
The Fatal Attraction Between Pro-Prion and Filamin A: Prion As a Marker in Human Cancers
Sy, M., Li, C., Yu, S., & Xin, W. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.14 · Cited by 18
Molecular Biomarkers in Colorectal Carcinoma
Puerta-García, E., Cañadas‐Garre, M., & Calleja‐Hernández, M. Á. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.63 · Cited by 21
KRAS mutation as a prognostic factor in ampullary adenocarcinoma: a meta-analysis and review
Kim, B. J., Jang, H. J., Kim, J. H., Kim, H. S., & Lee, J. (2016) · Oncotarget · doi:10.18632/oncotarget.11156 · Cited by 18
“KRAS gene is included in the mammalian Ras gene family and plays a key role in Ras/mitogen-activated protein kinase signaling [12].”
Background
PIK3CA mutations in KRAS and BRAF wild type colorectal cancer patients. A study of Spanish population
Herreros‐Villanueva, M., Gomez-Manero, N., Múñiz, P., Girón, C. G., & del Corral, M. J. C. (2010) · Molecular Biology Reports · doi:10.1007/s11033-010-0236-6 · Cited by 18
Visualizing Ras signalling in real-time
Walker, S. A., & Lockyer, P. J. (2004) · Journal of Cell Science · doi:10.1242/jcs.01285 · Cited by 18
“In 1980, pioneering work from Scolnick and colleagues (Willingham et al., 1980) demonstrated that H-Ras and K-Ras proteins are predominantly located on the inner leaflet of the plasma membrane in Harvey and Kirsten murine sarcoma virus (MSV)-transformed cells [see Malumbres and Barbacid (Malumbres and Barbacid, 2003)…”
BackgroundInfluential
Restoration of thrombospondin 1 expression in tumor cells harbouring mutant ras oncogene by treatment with low doses of doxycycline
Kałas, W., Gilpin, S. E., Yu, J., May, L. L., Krchnakova, H., BORNSTEIN, P. K., & Rak, J. W. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.08.128 · Cited by 18
E1a Gene Expression Blocks the ERK1/2 Signaling Pathway by Promoting Nuclear Localization and MKP Up-regulation
Callejas‐Valera, J. L., Guinea‐Viniegra, J., Ramírez‐Castillejo, C., Recio, J. A., Galán‐Moya, E. M., Martinez, N. J., Rojas, J. M., y Cajal, S. R., & Sánchez‐Prieto, R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709230200 · Cited by 18
Inter-cellular adhesion disruption and the RAS/RAF and beta-catenin signalling in lung cancer progression
Götz, R. (2008) · Cancer Cell International · doi:10.1186/1475-2867-8-7 · Cited by 19
“A high proportion of human cancers including those of the lung carry activating point mutations in RAS (Figure 2) [33].”
Natural products targeting RAS by multiple mechanisms and its therapeutic potential in cancer: An update since 2020
Liu, Y., Chen, J., Li, X., Fan, Y., Peng, C. Y., Ye, X., Wang, Y. A., & Xie, X. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107577 · Cited by 17
Conserved electrostatic fields at the Ras–effector interface measured through vibrational Stark effect spectroscopy explain the difference in tilt angle in the Ras binding domains of Raf and RalGDS
Walker, D. M., Wang, R., & Webb, L. J. (2014) · Physical Chemistry Chemical Physics · doi:10.1039/c4cp00743c · Cited by 17
The Coordination of Cell Growth during Fission Yeast Mating Requires Ras1-GTP Hydrolysis
Weston, C. A., Bond, M., Croft, W. D., & Ladds, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077487 · Cited by 17
“However, whilst much research into their affects on MAPK signaling has been undertaken [43], little appears to be known about oncogenic transitions and cell polarity.”
Background
MicroRNAs and Cancer
Trang, P., Weidhaas, J. B., & Slack, F. J. (2016) · Springer eBooks · doi:10.1007/978-1-59745-458-2_17 · Cited by 17
A quantitative structure-activity relationship (QSAR) study of some diaryl urea derivatives of B-RAF inhibitors
Hassanzadeh, F., Sadeghian-Rizi, S., & Sakhteman, A. (2016) · Research in Pharmaceutical Sciences · doi:10.4103/1735-5362.194869 · Cited by 17
“Numerous cancers are related to the constitutive activation of the above signaling pathway (3).”
NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions
Kim, J. H., Hong, J. H., Choi, Y., Lee, J. A., Seo, M.-K., Lee, M., An, S. B., Sung, M. J., Cho, N., Kim, S., et al. (2021) · The Journal of Pathology · doi:10.1002/path.5779 · Cited by 17
PLCε signaling in cancer
Zhang, R., Du, W., Zhang, Y., Zheng, J., & Pei, D. (2015) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-015-1999-x · Cited by 17
Regulation of Myosin Light Chain Kinase Expression by Angiotensin II in Hypertension
Han, Y.-J., Hu, W., Piano, M. R., & de Lanerolle, P. (2008) · American Journal of Hypertension · doi:10.1038/ajh.2008.199 · Cited by 17
The contribution of molecular epidemiology to the identification of human carcinogens: current status and future perspectives
Boffetta, P., & Islami, F. (2012) · Annals of Oncology · doi:10.1093/annonc/mds543 · Cited by 17
“Normal Ras proteins are involved in the control of several cellular functions, including proliferation, differentiation, and survival [50].”
Background
Understanding the Predictive Role of K-ras for Epidermal Growth Factor Receptor–Targeted Therapies in Colorectal Cancer
Ramos, F. J., Macarulla, T. M., Capdevila, J., Élez, E., & Tabernero, J. M. (2008) · Clinical Colorectal Cancer · doi:10.3816/ccc.2008.s.008 · Cited by 17
Ras proteins control mitochondrial biogenesis and function inSaccharomyces cerevisiae
Plecitá‐Hlavatá, L., & Nyström, T. (2003) · Folia Microbiologica · doi:10.1007/bf02931505 · Cited by 17
“They were later found in various carcinogen-induced animal tumor models, including human carcinomas (Malumbres and Barbacid 2003).”
Background
Global gene expression in Ha‐ras and B‐raf mutated mouse liver tumors
Jaworski, M., Ittrich, C., Hailfinger, S., von Bonin, M., Buchmann, A., Schwarz, M., & Köhle, C. (2007) · International Journal of Cancer · doi:10.1002/ijc.22801 · Cited by 17
From the bench to the bed: individualizing treatment in non-small-cell lung cancer
Santarpía, M., Altavilla, G., Salazar, F., Tarón, M., & Rosell, R. (2006) · Clinical & Translational Oncology · doi:10.1007/s12094-006-0161-2 · Cited by 17
HSPB8 counteracts tumor activity of BRAF- and NRAS-mutant melanoma cells by modulation of RAS-prenylation and autophagy
Cristofani, R., Piccolella, M., Marelli, M. M., Tedesco, B., Poletti, A., & Moretti, R. M. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05365-9 · Cited by 16
“NRAS, the first oncogene identified in melanoma, is the one predominantly mutated among the RAS isoforms in melanoma (15–30% of cases) [9].”
Background
Application of organoid culture from HPV18 ‐positive small cell carcinoma of the uterine cervix for precision medicine
Kusakabe, M., Taguchi, A., Tanikawa, M., Hoshi, D., Tsuchimochi, S., Qian, X., Toyohara, Y., Kawata, A., Wagatsuma, R., Yamaguchi, K., et al. (2023) · Cancer Medicine · doi:10.1002/cam4.5588 · Cited by 16
Computational design and validation of effective siRNAs to silence oncogenic KRAS
Ramalingam, P. S., & Arumugam, S. (2023) · 3 Biotech · doi:10.1007/s13205-023-03767-w · Cited by 18
“RAS has three isoforms namely Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), Neuroblastoma RAS viral oncogene homolog (NRAS), and Harvey Rat sarcoma virus (HRAS) whose mutation frequencies are about 85%, 14%, and 1% respectively (Harvey 1964; Kirsten et al. 1970; Malumbres and Barbacid 2003).”
Background
DIRAS3 induces autophagy and enhances sensitivity to anti-autophagic therapy in KRAS-driven pancreatic and ovarian carcinomas
Bildik, G., Gray, J. P., Mao, W., Yang, H., Özyurt, R., Orellana, V. R., Wever, O. D., Carey, M. S., Bast, R. C., & Lü, Z. (2024) · Autophagy · doi:10.1080/15548627.2023.2299516 · Cited by 16
“The RAS family of proto-oncogenes, including KRAS, NRAS, and HRAS are GTPases localized in the cell membrane that regulate cell proliferation, motility, and apoptosis [1–3].”
Background
An updated overview of K-RAS G12C inhibitors in advanced stage non-small cell lung cancer
Tenekeci, A. K., Unal, A. A., Ceylan, F., & Sendur, M. A. N. (2024) · Future Oncology · doi:10.1080/14796694.2024.2407280 · Cited by 16
Phosphoproteomic analysis of basal and therapy‐induced adaptive signaling networks in BRAF and NRAS mutant melanoma
Smalley, I., Fang, B., Munko, A., Gibney, G. T., Koomen, J. M., & Smalley, K. S. M. (2014) · PROTEOMICS · doi:10.1002/pmic.201400200 · Cited by 16
“Although not explored as extensively, Ras may regulate cell motility in different ways—such as through direct modulation of small Gproteins involved in cytoskeletal control like Rho, Rac, and CDC42 [41].”
Background
Paxillin Enables Attachment-independent Tyrosine Phosphorylation of Focal Adhesion Kinase and Transformation by RAS
Wade, R., Brimer, N., Lyons, C. E., & Pol, S. V. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.294504 · Cited by 16
Soil quality in the Lomellina area using in vitro models and ecotoxicological assays
Baderna, D., Colombo, A., Romeo, M., Cambria, F., Teoldi, F., Lodi, M., Diomede, L., & Benfenati, E. (2014) · Environmental Research · doi:10.1016/j.envres.2014.05.030 · Cited by 17
“a Martignon (2009). b Adapted from Kapustuka et al.”
Background
Integration of multiple signaling pathway activities resolves K-RAS/N-RAS mutation paradox in colon epithelial cell response to inflammatory cytokine stimulation
Kreeger, P. K., Wang, Y., Haigis, K. M., & Lauffenburger, D. A. (2010) · Integrative Biology · doi:10.1039/b925935j · Cited by 16
In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations
Porta, M. S., López‐Jiménez, T., Pumarega, J. A., Jariod, M., Crous‐Bou, M., Marco, E., Rifà, J., Grimalt, J. O., Malats, N., Real, F. X., et al. (2009) · Mutagenesis · doi:10.1093/mutage/gep037 · Cited by 16
“Yet, a complete understanding of ras function is still to come (1) and ‘concepts that once seemed on the verge of comprehension have evolved such that elegant complexity coupled with hopeless confusion better defines our current state of knowledge’ (2).”
Background
Activated N-Ras signaling regulates arterial-venous specification in zebrafish
Ren, C., Wang, L., Jia, X., Liu, Y., Dong, Z., Jin, Y., Chen, Y., Deng, M., Zhou, Y., Zhou, Y., et al. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-34 · Cited by 16
“As Ras signaling has been proved to be important for cell proliferation [1,2], the frequencies of endothelial cells in the hNRASD12;flk1:GFP and control;flk1:GFP embryos at 28 hpf were respectively quantified by flow cytometry analysis, and the result showed no significant difference in the frequencies of GFP endothel…”
BackgroundMethod
Knowledge-based modeling of peptides at protein interfaces: PiPreD
Oliva, B., & Fernández‐Fuentes, N. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu838 · Cited by 15
“One of such example is that of RAS, an important protein family involved in the regulation of signaling pathways linked to cell grow and proliferation (Malumbres and Barbacid, 2003), which interact with a range of protein effectors through a common interface called the switch I–II region (Milburn et al.”
Background
Targeting the MEK signaling pathway in non-small cell lung cancer (NSCLC) patients with RAS aberrations
Abdel-Rahman, O. M. (2016) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465816632111 · Cited by 17
KRAS insertion mutations are oncogenic and exhibit distinct functional properties
White, Y. N., Bagchi, A., Ziffle, J. V., Sheth, A. I., Bollag, G. E., Zhang, C., Carias, H., Dickens, D. S., Loh, M. L., Shannon, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms10647 · Cited by 16
Targeting Mutant KRAS for Anticancer Therapy
Chen, F., Alphonse, M. P., Liu, Y., & Liu, Q. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190902151307 · Cited by 15
NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma
Hu, W., Liu, Z., Salato, V. K., North, P. E., Bischoff, J. E., Kumar, S. N., Fang, Z. H., Rajan, S., Hussain, M. M., & Miao, Q. (2021) · JCI Insight · doi:10.1172/jci.insight.142299 · Cited by 16
“The aberrant activation of RAS signaling is associated with human vascular diseases such as hematological malignancies and vascular disorders (45, 46).”
Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A
Aguila, E. M. D., Tang, X., & Gudas, L. J. (2022) · Oncology Research and Treatment · doi:10.1159/000522425 · Cited by 18
Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations
Zeng, J., Chen, J., Xia, F., Cui, Q., Deng, X., & Xu, X. (2022) · Physical Chemistry Chemical Physics · doi:10.1039/d2cp00274d · Cited by 15
Polyisoprenylated methylated protein methyl esterase: A putative biomarker and therapeutic target for pancreatic cancer
Aguilar, B. J., Nkembo, A. T., Duverna, R., Poku, R. A., Amissah, F., Ablordeppey, S. Y., & Lamango, N. S. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.05.018 · Cited by 16
Synthese und Anwendung fluoreszenzmarkierter Ras‐Proteine in der Bildgebung lebender Zellen
Reents, R., Wagner, M., Kuhlmann, J., & Waldmann, H. (2004) · Angewandte Chemie · doi:10.1002/ange.200353265 · Cited by 16
Study human pancreatic cancer in mice: How close are they?
Zhang, Y., Chen, L. L., Yang, J., Fleming, J. B., Chiao, P. J., Logsdon, C. D., & Li, M. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.11.001 · Cited by 16
“KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is the best known oncogene in pancreatic cancer involved in cell proliferation, survival, and differentiation [7,8].”
An in silico study of the molecular basis of B-RAF activation and conformational stability
Fratev, F., & Jónsdóttir, S. Ó. (2009) · BMC Structural Biology · doi:10.1186/1472-6807-9-47 · Cited by 16
“B-RAF, a member of the RAF kinase family, is an important new therapeutic target for a group of human cancers, as it constitutes activation of the RAFMEK-ERK pathway common to numerous cancers [1].”
Background
MAPK activation in mature cataract associated with Noonan syndrome
Hashida, N., Ping, X., & Nishida, K. (2013) · BMC Ophthalmology · doi:10.1186/1471-2415-13-70 · Cited by 14
“The RAS/RAF/MEK/ERK pathway is the classical RAS-MAPK signaling pathway implicated in growth-factor mediated cell proliferation, differentiation, and death [16].”
Background

Authors: Malumbres, M., & Barbacid, M.
Affiliations: Spanish National Cancer Research Centre (ES)
Corresponding author: Malumbres, Marcos
Barbacid, Mariano
ORCID: Malumbres, Marcos
Barbacid, Mariano
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2003-06-01
Volume: 3
Issue: 6
Pages: 459-465
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc1097
OpenAlex: W2083695927
Cited by: 1,902
References: 122
Citations by year: 2026: 39 · 2025: 77 · 2024: 94 · 2023: 84 · 2022: 89 · 2021: 78 · 2020: 68 · 2019: 74 · 2018: 80 · 2017: 99 · 2016: 91 · 2015: 98 · 2014: 117 · 2013: 120 · 2012: 104
FWCI: 3.49
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords: oncogenic Ras, signal transduction, molecular oncology, RAS inhibitors, cancer therapy
MeSH terms: Animals, Humans, Genes, ras, Biomedical Research, History, 20th Century, History, 21st Century

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

RAS oncogenes: the first 30 years

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks