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A Comprehensive Survey of Ras Mutations in Cancer
Open accessAbstract
All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers. Cancer Res; 72(10); 2457–67. ©2012 AACR.
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“Approximately 90% of PDAC cases harbor a Kirsten rat sarcoma (KRAS) mutation (Prior et al., 2012).”
From The antitumoral effect of statins in pancreatic ductal adenocarcinoma: a scoping review (2026) · cites this paper as Prior et al., 2012
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“This specific mutation, present in ~3% of CRC cases, 2 is associated with significantly reduced progression-free survival (PFS) and overall survival (OS) compared to KRAS wildtype tumors.[3][4][5]”
From Garsorasib, a KRAS G12C inhibitor, with or without cetuximab, an EGFR antibody, in colorectal cancer cohorts of a phase II trial in advanced solid tumors with KRAS G12C mutation (2025) · cites this paper as [2]
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“Unlike other clinically actionable genomic alterations found in NSCLCs (such as EGFR and ALK aberrations), KRAS mutations, particularly KRASG12C and KRASG12V, are strongly associated with smoking29–31.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [29]
In the citing paper
“However, RAS mutations and the resulting deregulated signaling events are responsible for one third of all human cancers4 (Figure 1).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [4]
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“Overall, KRAS is mutated in many cancers (predominantly adenocarcinomas), whereas NRAS mutations are prominent in melanoma and myeloid cancer4,15,16 (Fig. 1).”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [4]
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“The basis of the specific G12X mutation frequencies has remained unclear, except for the G12C transversion mutation (c.34G>T) associated with smoking in lung cancer [6,7].”
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Citations
Cites
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278
The Guanine Nucleotide-Binding Switch in Three Dimensions
Vetter, I. R., & Wittinghofer, A. (2001) · Science · doi:10.1126/science.1062023 · Cited by 1,875
Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53
Denissenko, M. F., Pao, A., Tang, M.-S., & Pfeifer, G. P. (1996) · Science · doi:10.1126/science.274.5286.430 · Cited by 1,650
Tobacco carcinogens, their biomarkers and tobacco-induced cancer
Hecht, S. S. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1190 · Cited by 1,551
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants
Scheffzek, K., Ahmadian, M. R., Kabsch, W., Wiesmüller, L., Lautwein, A., Schmitz, F., & Wittinghofer, A. (1997) · Science · doi:10.1126/science.277.5324.333 · Cited by 1,543
Zarbl, H., Sukumar, S. V., Arthur, A. V., Martı́n-Zanca, D., & Barbacid, M. (1985) · Nature · doi:10.1038/315382a0 · Cited by 807
The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation
Tidyman, W. E., & Rauen, K. A. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.001 · Cited by 799
Endomembrane Trafficking of Ras
Choy, E., Chiu, V. K., Silletti, J., Feoktistov, M., Morimoto, T., Michaelson, D., Ivanov, I. E., & Philips, M. R. (1999) · Cell · doi:10.1016/s0092-8674(00)80607-8 · Cited by 754
De Roock, W., Jonker, D. J., Di Nicolantonio, F., Sartore-Bianchi, A., Tu, D., Siena, S., Lamba, S., Arena, S., Frattini, M., Piessevaux, H., et al. (2010) · JAMA · doi:10.1001/jama.2010.1535 · Cited by 748
Cited by
Sorted by citations
Items 601–700 of 1,006
Ouerhani, S., Bougatef, K., Soltani, I., Elgaaïed, A. B. A., Abbès, S., & Menif, S. (2013) · Molecular Biology Reports · doi:10.1007/s11033-013-2512-8 · Cited by 35
“These results were consistent with other studies which have reported that 80 % of KRAS mutations occur at codon 12 [5].”
InfluentialMüller, M. P., Jeganathan�, S., Heidrich, A., Campos, J., & Goody, R. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-03973-6 · Cited by 36
“= ⋅ + ⋅ k k [GDP] k [mdGDP] (1) obs GDP mdGDP”
Isoform-specific Ras signaling is growth factor dependent
Hood, F. E., Klinger, B., Newlaczyl, A. U., Sieber, A., Dorel, M., Oliver, S. P., Coulson, J. M., Blüthgen, N., & Prior, I. A. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-10-0676 · Cited by 35
Self-citationGlutaminase inhibition as potential cancer therapeutics: current status and future applications
Cyriac, R., & Lee, K. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2290911 · Cited by 38
“44 Studies have revealed that the KRAS and Myc oncogenes increase glutamine addiction and glycolysis, which divert glucose from the TCA cycle.”
pMD-Membrane: A Method for Ligand Binding Site Identification in Membrane-Bound Proteins
Prakash, P., Sayyed–Ahmad, A., & Gorfe, A. A. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004469 · Cited by 36
“This is because, as we alluded to above, different Ras isoforms are associated with distinct cancer types [29] despite the fact that they share a catalytic domain that is nearly identical in sequence and average structure [17,43].”
BackgroundThe Nogo-B receptor promotes Ras plasma membrane localization and activation
Zhao, B., Hu, W., Kumar, S. N., Gonyo, P., Rana, U., Liu, Z., Wang, B., Duong, W. Q., Yang, Z., Williams, C. L., et al. (2017) · Oncogene · doi:10.1038/onc.2016.484 · Cited by 34
“23, 46 , oncogenic signaling by Ras contributes to the tumorigenic and invasive potential of breast epithelial cells 23, 30 .”
Hata, A. N., Rowley, S. C., Archibald, H. L., Gomez‐Caraballo, M., Siddiqui, F. M., Ji, F., Jung, J., Light, M. E., Lee, J. S., Debüssche, L., et al. (2017) · Oncogene · doi:10.1038/onc.2017.258 · Cited by 35
“In contrast, there are no approved targeted therapies for cancers that harbor KRAS mutations, which occur in 15–20% of NSCLCs, 30–35% of colorectal cancers (CRC) and the majority of pancreatic cancers (5).”
Zhang, X., Cao, J., Miller, S. P., Jing, H., & Lin, H. (2017) · ACS Central Science · doi:10.1021/acscentsci.7b00440 · Cited by 36
Kim, Y. J., Chambers, A. G., Cecchi, F., & Hembrough, T. (2018) · Journal of Proteomics · doi:10.1016/j.jprot.2018.04.022 · Cited by 34
Kota, S., Hou, S., Guerrant, W., Madoux, F., Troutman, S. A., Fernández-Vega, V., Alekseeva, N., Madala, N., Scampavia, L. D., Kissil, J. L., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0257-5 · Cited by 35
“NRAS mutations are found mostly in melanoma (>30%) and multiple myeloma (18%) [3].”
Fuentes, N. R., Mlih, M., Barhoumi, R., Fan, Y., Hardin, P. E., Steele, T. J., Behmer, S. T., Prior, I. A., Karpac, J., & Chapkin, R. S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0324 · Cited by 34
“This particular KRas variant was chosen because one third of colorectal tumors harbor KRASmutations and approximately 80% of these mutations are at codon 12, while the remaining mutations are at codon 13 (38).”
BackgroundSelf-citationAllosteric KRas4B Can Modulate SOS1 Fast and Slow Ras Activation Cycles
Liao, T.-J., Jang, H., Fushman, D., & Nussinov, R. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2018.07.016 · Cited by 34
“Among the three HRas, NRas, and KRas isoforms, KRas is the most frequently mutated in RAS-driven cancers (3,4).”
BackgroundSirt1 protects from K‐Ras‐driven lung carcinogenesis
Costa‐Machado, L. F., Martín‐Hernández, R., Sánchez‐Luengo, M. Á., Hess, K., Vales‐Villamarín, C., Barradas, M., Lynch, C. J., de la Nava, D., Díaz‐Ruiz, A., de Cabo, R., et al. (2018) · EMBO Reports · doi:10.15252/embr.201643879 · Cited by 34
“As K-Ras is the member of the Ras family most frequently mutated in human cancer [39,40], we decided to test whether K-Ras could be responsible for the downregulation of Sirt1 during chronic mitogenic stimulation.”
Cimino, P. J., Huang, L., Du, L., Wu, Y., Bishop, J., Dalsing-Hernandez, J. E., Kotlarczyk, K. L., Gonzales, P. A., Carew, J. S., Nawrocki, S. T., et al. (2019) · Biomedical Reports · doi:10.3892/br.2019.1196 · Cited by 34
“Activating point mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) are present in ~30% of human cancer, including the vast majority of types of pancreatic cancer and large fractions of lung, colon and breast cancer (1).”
BackgroundSakane, T., Murase, T., Okuda, K., Saida, K., Masaki, A., Yamada, T., Saito, Y., Nakanishi, R., & Inagaki, H. (2019) · Histopathology · doi:10.1111/his.13936 · Cited by 34
Liu, Y., Feng, W., Gu, S., Wang, H., Zhang, Y., Chen, W., Xu, W., Chen, L., Gong, A., & Xu, M. (2019) · Europe PMC (PubMed Central) · Cited by 34
Zinkus-Boltz, J., Devalk, C., & Dickinson, B. C. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00669 · Cited by 35
Rho-ROCK Signaling in Normal Physiology and as a Key Player in Shaping the Tumor Microenvironment
Porazinski, S. R., Parkin, A., & Pajic, M. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-35582-1_6 · Cited by 34
Targeting NRAS-Mutant Cancers with the Selective STK19 Kinase Inhibitor Chelidonine
Qian, L. M., Chen, K., Wang, C., Chen, Z., Meng, Z., & Wang, P. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2604 · Cited by 34
“KRAS, HRAS, and NRAS (1, 3, 8, 9) were the first identified oncogenes, and it is now well established that about 25% of all human cancers harbor activating mutations in at least one of these proteins (8, 36).”
BackgroundRAS Nanoclusters: Dynamic Signaling Platforms Amenable to Therapeutic Intervention
Van, Q. N., Prakash, P., Shrestha, R., Balius, T. E., Turbyville, T. J., & Stephen, A. G. (2021) · Biomolecules · doi:10.3390/biom11030377 · Cited by 34
“, G12, G13, Q61) are found in 20% of human cancers [1,2].”
BackgroundSmall molecule Son of Sevenless 1 (SOS1) inhibitors: a review of the patent literature
Thompson, S. K., Buckl, A. K., Dossetter, A. G., Griffen, E., & Gill, A. L. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1952984 · Cited by 35
Divergent Mechanisms Activating RAS and Small GTPases Through Post-translational Modification
Osaka, N., Hirota, Y., Ito, D., Ikeda, Y., Kamata, R., Fujii, Y., Chirasani, V. R., Campbell, S. L., Takeuchi, K., Senda, T., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.707439 · Cited by 35
“Among them, the K-RAS G12C oncogenic mutation is present in about 3–14% of cancer patients (Prior et al., 2012; Prior et al., 2020; Nassar et al., 2021) and has been targeted for drug discovery efforts (Ostrem et al.”
BackgroundDysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk
Erazo‐Oliveras, A., Muñoz‐Vega, M., Salinas, M. L., Wang, X., & Chapkin, R. S. (2022) · FEBS Journal · doi:10.1111/febs.16665 · Cited by 38
Lymphatic vessel abnormalities arising from disorders of Ras signal transduction
Sevick-Muraca, E. M., & King, P. D. (2013) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2013.09.004 · Cited by 34
“Thus, somatic activating mutations in Ras that render it refractory to inactivation by RasGAPs are found in 30% of all human cancers (Prior et al. 2012).”
BackgroundBarceló, C., Paco, N., Beckett, A. J., Alvarez-Moya, B., Garrido, E., Gelabert, M., Tebar, F., Jaumot, M., Prior, I. A., & Agell, N. (2013) · Journal of Cell Science · doi:10.1242/jcs.123737 · Cited by 34
“These mutations, which give rise to a protein that is defective in GTP hydrolysis and, therefore, remains constitutively active in a GTPbound form, have been detected in each of the three closely related human Ras genes (HRAS, NRAS and KRAS).”
BackgroundSelf-citationTumour promoting and suppressing roles of the atypical MAP kinase signalling pathway ERK3/4-MK5
Kostenko, S., Dumitriu, G., & Moens, U. L. (2012) · Journal of Molecular Signaling · doi:10.1186/1750-2187-7-9 · Cited by 38
“The ras, raf and c-myc genes are amongst the most commonly mutated genes in cancer [58,87,88].”
BackgroundRas sumoylation in cell signaling and transformation
Dai, W., Xie, S., Chen, C., & Choi, B. H. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.033 · Cited by 27
Johansen, K. H., Golec, D. P., Okkenhaug, K., & Schwartzberg, P. L. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.09.002 · Cited by 33
Camps-Fajol, C., Cavero, D., Minguillón, J., & Surrallés, J. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107544 · Cited by 36
Wen, L., & Xie, M. (2016) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2016.08.013 · Cited by 33
Biancucci, M., Dolores, J. S., Wong-Roushar, J., Grimshaw, S., Anderson, W. F., Satchell, K. J. F., & Kwon, K. (2017) · BMC Biotechnology · doi:10.1186/s12896-016-0323-4 · Cited by 33
“To test for successful purification of a eukaryotic protein, Ras, a human oncoprotein involved in the regulation of cell proliferation, differentiation and survival [25, 26].”
BackgroundStein, C. K., Pawlyn, C., Chavan, S. S., Rasche, L., Weinhold, N., Corken, A. L., Buros, A. F., Sonneveld, P., Jackson, G. H., Landgren, O., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15718 · Cited by 32
“While mutations at Q61 compose 60% of NRAS mutations in other cancers [14], we find this rate to be over 80% in MM likely due to the increased rate of NRAS mutations at Q61 observed in HRD and t(11;14) myeloma—subgroups that comprise the majority of MM.”
BackgroundPadala, R. R., Karnawat, R., Viswanathan, S. B., Thakkar, A. V., & Das, A. B. (2017) · Molecular BioSystems · doi:10.1039/c6mb00786d · Cited by 33
Are Parallel Proliferation Pathways Redundant?
Nussinov, R., Tsai, C., & Jang, H. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.03.013 · Cited by 33
Chen, K., Shang, Z., Dai, A.-L., & Dai, P.-L. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117816 · Cited by 33
Sarkar, D., Olejniczak, E. T., Phan, J., Coker, J. A., Sai, J., Arnold, A. L., Beesetty, Y., Waterson, A. G., & Fesik, S. W. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00511 · Cited by 33
Kumar, S. U., Bithia, R., Kumar, D. T., Doss, C. G. P., & Zayed, H. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1830177 · Cited by 32
“Allelic mutations that replace the amino acid Gly in the 12th position to Ala, Cys, Asp, Arg, Ser, and Val are reported in colorectal, lung, pancreatic, colon, bladder, and gastric carcinomas (Figure 1) (Karachaliou et al., 2013; Prior et al., 2012).”
BackgroundDas, D., Wang, J., & Hong, J. (2021) · ChemMedChem · doi:10.1002/cmdc.202100166 · Cited by 35
Munck, J. M., Berdini, V., Bevan, L., Brothwood, J. L., Castro, J., Courtin, A., East, C., Ferraldeschi, R., Heightman, T. D., Hindley, C. J., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0909 · Cited by 33
Small molecule drugs with immunomodulatory effects in cancer
Murphy, A. G., & Zheng, L. (2015) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2015.1057363 · Cited by 33
“Genes encoding RAS (KRAS, NRAS, HRAS) are among the most frequently mutated genes in cancer including biliary tract (33%), large bowel (36%), esophageal (5%), pancreatic (63%) and gastric cancer (12%).(33) Dysregulation of the MAPK pathway is associated with effects on the immune system.”
BackgroundQuantitative Measurement of Intrinsic GTP Hydrolysis for Carcinogenic Glutamine 61 Mutants in H-Ras
Novelli, E. T., First, J. T., & Webb, L. J. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00878 · Cited by 33
Akt and SGK protein kinases are required for efficient feeding by macropinocytosis
Williams, T. D., Peak‐Chew, S., Paschke, P., & Kay, R. R. (2019) · Journal of Cell Science · doi:10.1242/jcs.224998 · Cited by 30
“Ras proteins are especially frequently mutated with, strikingly, ∼95% of pancreatic cancers driven by K-Ras (Fernandez-Medarde and Santos, 2011; Kandoth et al., 2013; Prior et al., 2012; Waddell et al., 2015).”
BackgroundStructural insights into small-molecule KRAS inhibitors for targeting KRAS mutant cancers
Pandey, D., Chauhan, S. C., Kashyap, V. K., & Roy, K. K. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116771 · Cited by 32
Exploration of Cryptic Pockets Using Enhanced Sampling Along Normal Modes: A Case Study of KRAS G12D
Vithani, N., Zhang, S., Thompson, J. P., Patel, L. A., Demidov, A., Xia, J., Balaeff, A., Mentes, A., Arnautova, Y. A., Kohlmann, A., et al. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c01435 · Cited by 40
Oral reovirus reshapes the gut microbiome and enhances antitumor immunity in colon cancer
Lee, W. S., Lee, S. J., Lee, H. J., Yang, H., Go, E., Enkhtaivan, G., Song, K., Xiang, X., Park, D.-G., Alain, T., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53347-6 · Cited by 34
“Moreover, dysregulation of RAS, TP53, and RB signaling pathways in cancer cells increases their susceptibility to viral infection 10,11 .”
Jauhri, M., Bhatnagar, A., Gupta, S., Shokeen, Y., Minhas, S., & Aggarwal, S. (2016) · Medical Oncology · doi:10.1007/s12032-016-0820-2 · Cited by 32
Targeting the α4-α5 interface of RAS results in multiple levels of inhibition
Spencer-Smith, R., Li, L., Prasad, S., Koide, A., Koide, S., & O’Bryan, J. P. (2017) · Small GTPases · doi:10.1080/21541248.2017.1333188 · Cited by 32
“KRAS is the most frequently mutated RAS isoform in human cancers, with mutations predominating in cancers of the pancreas, lung, and colon.(1,5,6) For these reasons RAS has become one of the highest priority tar-”
BackgroundZhuang, R., Li, S., Li, Q., Guo, X., Shen, F., Sun, H., & Liu, T. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182562 · Cited by 32
“KRAS mutation is one of the most frequent molecular abnormalities found in several types of cancer such as pancreatic cancer, colorectal cancer, non-small cell lung cancer [47].”
BackgroundBaum, J. E., Sung, K.-J., Tran, H., Song, W., & Ginter, P. S. (2018) · International Journal of Surgical Pathology · doi:10.1177/1066896918821182 · Cited by 32
Kim, Y., Baek, D.-S., Lee, S., Park, D., Kang, H. N., Cho, B. C., & Kim, Y. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.09.005 · Cited by 31
Pumping the brakes on RAS – negative regulators and death effectors of RAS
Stewart, D. R. H., & Clark, G. J. (2020) · Journal of Cell Science · doi:10.1242/jcs.238865 · Cited by 35
Torres, M., Rosselló, C. A., Fernández‐García, P., Lladó, V., Kakhlon, O., & Escribá, P. V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072322 · Cited by 35
“The RAS family of amphitropic proteins are mutated (especially K-RAS) in 95% of pancreatic, 45% of colorectal, and 35% of lung cancers [117].”
BackgroundPathogenesis of bowel endometriosis
Yong, P. J., Bedaiwy, M. A., Alotaibi, F. T., & Anglesio, M. S. (2020) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2020.05.009 · Cited by 35
Moeng, S., Son, S. W., Lee, J. S., Lee, H. Y., Kim, T. H., Choi, S. Y., Kuh, H. J., & Park, J. K. (2020) · Biomedicines · doi:10.3390/biomedicines8080267 · Cited by 31
WIDOCK: a reactive docking protocol for virtual screening of covalent inhibitors
Scarpino, A., Petri, L., Knez, D., Imre, T., Ábrányi‐Balogh, P., Ferenczy, G. G., Gobec, S., & Keserű, G. M. (2021) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-020-00371-5 · Cited by 34
“The G12C mutation has been shown to reduce the GTP/GDP exchange rate and consequently hyperactivates the enzyme causing abnormal cell growth [26].”
BackgroundHa, D. P., Huang, B., Wang, H., Rangel, D. F., Krieken, R. V., Liu, Z., Samanta, S., Neamati, N., & Lee, A. S. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100837 · Cited by 33
Bousquet, M. S., Ma, J., Ratnayake, R., Havre, P. A., Yao, J. G., Dang, N. H., Paul, V. J., Carney, T. J., Dang, L. H., & Luesch, H. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.5b00860 · Cited by 31
Taunk, N. K., Oh, J. H., Shukla‐Dave, A., Beal, K. P., Vachha, B. A., Holodny, A. I., & Hatzoglou, V. (2017) · Neuro-Oncology · doi:10.1093/neuonc/nox159 · Cited by 32
The RAL Enigma: Distinct Roles of RALA and RALB in Cancer
Richardson, D. S., Spehar, J. M., Han, D. T., Chakravarthy, P. A., & Sizemore, S. T. (2022) · Cells · doi:10.3390/cells11101645 · Cited by 31
Sabe, H. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01130-3 · Cited by 29
“KRAS mutations are predominant in cancer, particularly in PDAC, and 90% to 95% of PDACs have this mutation [1, 5].”
BackgroundMir, S. A., Nayak, B., Aljarba, N. H., Kumarasamy, V., Subramaniyan, V., & Dhara, B. (2024) · ACS Omega · doi:10.1021/acsomega.4c02671 · Cited by 31
“3,4 These mutations induce a state of constitutive activation in the KRas protein, disrupting its normal regulatory functions.”
BackgroundNussinov, R. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169044 · Cited by 34
Bender, R. H. F., Haigis, K. M., & Gutmann, D. H. (2015) · Stem Cells · doi:10.1002/stem.1990 · Cited by 31
Prakash, P., & Gorfe, A. A. (2014) · Molecular Simulation · doi:10.1080/08927022.2014.895000 · Cited by 31
Buoncervello, M., Romagnoli, G., Buccarelli, M., Fragale, A., Toschi, E., Parlato, S., Lucchetti, D., Macchia, D., Spada, M., Canini, I., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8379 · Cited by 31
“Epigenetic mechanisms are linked to isoform-specific KRAS proteins, that drive different cancer programs by modulation of diverse downstream signaling pathways [46].”
RASSF5: An MST activator and tumor suppressor in vivo but opposite in vitro
Liao, T.-J., Tsai, C., Jang, H., Fushman, D., & Nussinov, R. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.09.001 · Cited by 30
Zhu, W., Gliddon, B. L., Jarman, K. E., Moretti, P. A. B., Tin, T., Parise, L. V., Woodcock, J. M., Powell, J. A., Ruszkiewicz, A. R., Pitman, M. R., et al. (2016) · Oncogene · doi:10.1038/onc.2016.428 · Cited by 31
Mehaffey, M. R., Schardon, C. L., Novelli, E. T., Cammarata, M. B., Webb, L. J., Fast, W. L., & Brodbelt, J. S. (2019) · Chemical Science · doi:10.1039/c9sc01032g · Cited by 31
Synthetic lethality: a step forward for personalized medicine in cancer
Jariyal, H., Weinberg, F. D., Achreja, A., Nagarath, D., & Srivastava, A. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.11.014 · Cited by 30
RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics
Kattan, W. E., & Hancock, J. F. (2020) · Biochemical Journal · doi:10.1042/bcj20190839 · Cited by 33
Biological significance of KRAS mutant allele expression in ovarian endometriosis
Yachida, N., Yoshihara, K., Suda, K., Nakaoka, H., Ueda, H., Sugino, K., Yamaguchi, M., Mori, Y., Yamawaki, K., Tamura, R., et al. (2021) · Cancer Science · doi:10.1111/cas.14871 · Cited by 32
Zebrafish Cancer Predisposition Models
Kobar, K., Collett, K., Prykhozhij, S. V., & Berman, J. N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.660069 · Cited by 34
Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor
Lim, S. M., Westover, K. D., Ficarro, S. B., Harrison, R. A., Choi, H. G., Pacold, M. E., Carrasco, M. A., Hunter, J., Kim, N. D., Xie, T., et al. (2013) · Angewandte Chemie · doi:10.1002/ange.201307387 · Cited by 30
Genome editing via non-viral delivery platforms: current progress in personalized cancer therapy
Lan, T., Que, H., Luo, M., Zhao, X., & Wei, X. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01550-8 · Cited by 31
The Morpho-Molecular Landscape of Spitz Neoplasms
Pozzo, C. A. D., & Cappellesso, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084211 · Cited by 31
“These proteins are implicated in the signal transduction from the cell surface to the nucleus through the PI3K-AKT and RAF-MEK1/2-ERK1/2 pathways stimulating growth, differentiation, proliferation, and survival of the cell [40,41].”
BackgroundComputed cancer interactome explains the effects of somatic mutations in cancers
Zhang, J., Pei, J., Durham, J., Bos, T., & Cong, Q. (2022) · Protein Science · doi:10.1002/pro.4479 · Cited by 31
“Gain-of-function SMMs in oncogene products such as BRAF and RAS [77, 78] are frequently observed in certain cancers as they promote cell growth through the RAS/RAF/ERK pathway.”
BackgroundRecent progress in targeting KRAS mutant cancers with covalent G12C-specific inhibitors
Rathod, L. S., Dabhade, P. S., & Mokale, S. N. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103557 · Cited by 32
Allosteric regulation of the 20S proteasome by the Catalytic Core Regulators (CCRs) family
Deshmukh, F. K., Ben‐Nissan, G., Olshina, M. A., Füzesi-Levi, M. G., Polkinghorn, C. R., Arkind, G., Leushkin, Y., Fainer, I., Fleishman, S. J., Tawfik, D. S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38404-w · Cited by 29
“Similar results were obtained when we analyzed the known cancer-associated mutations of the CCR NRas, G12D, G13R, or Q61R 33,34 (Supplementary Fig.3c).”
Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib)
El‐Hoss, J., Kolind, M. P., Jackson, M. T., Deo, N., Mikulec, K., McDonald, M. M., Little, C. B., Little, D. G., & Schindeler, A. (2013) · Bone · doi:10.1016/j.bone.2013.11.013 · Cited by 31
“The Ras–Raf–MEK–ERK axis (also called the Ras–MAPK pathway) has a central role in cell signaling, and is activated inmanyhuman cancers [1].”
BackgroundOncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer
Cheng, D. K., Oni, T. E., Thalappillil, J. S., Park, Y., Ting, H.-C., Alagesan, B., Prasad, N. V., Addison, K., Rivera, K. D., Pappin, D. J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016904118 · Cited by 30
“Thus far, direct inhibitors against KRAS have only successfully targeted the G12C mutant, which comprises 2.9% of KRAS mutant PDAC (21, 33).”
InfluentialClinical and functional spectrum of RAC2-related immunodeficiency
Donkó, Á., Sharapova, S. O., Kabát, J., Ganesan, S., Hauck, F. H., Bergerson, J., Marois, L., Abbott, J. K., Moshous, D., Williams, K. W., et al. (2024) · Blood · doi:10.1182/blood.2023022098 · Cited by 30
Navarro-Jiménez, M., González, B., Mulet-Margalef, N., Hierro, C., & Alonso, S. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-01166-3 · Cited by 38
“The forces that drive speci fi c mutations in RAS genes to dominate over others result from a complex interplay of factors, including tissue-speci fi c aspects such as genotoxic stress, biological selection, genomic topology, gene expression, and cellular context 9,10 .”
The impact of TP53 and RAS mutations on cerebellar glioblastomas
Milinković, V., Skender-Gazibara, M., Manojlović-Gačić, E., Gazibara, T. M., & Tanić, N. (2014) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2014.07.009 · Cited by 30
K-Ras4B/calmodulin/PI3Kα: A promising new adenocarcinoma-specific drug target?
Nussinov, R., Muratcioğlu, S., Tsai, C., Jang, H., Gürsoy, A., & Keskin, Ö. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1135131 · Cited by 30
Ni, D., Song, K., Zhang, J., & Lu, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112249 · Cited by 30
CPNE1 silencing inhibits the proliferation, invasion and migration of human osteosarcoma cells
Jiang, Z., Jiang, J., Zhao, B., Yang, H., Wang, Y., Guo, S., Deng, Y., Lu, D., Ma, T., Wang, H., et al. (2017) · Oncology Reports · doi:10.3892/or.2017.6128 · Cited by 30
Coding Molecular Determinants of Thyroid Cancer Development and Progression
Valvo, V., & Nucera, C. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.10.003 · Cited by 31
Toyama, Y., Kontani, K., Katada, T., & Shimada, I. (2019) · Science Advances · doi:10.1126/sciadv.aav8945 · Cited by 30
Aristolochic acid-induced genotoxicity and toxicogenomic changes in rodents
Mei, N., Li, X., Guo, X., Wang, H., & Chen, T. (2019) · World Journal of Traditional Chinese Medicine · doi:10.4103/wjtcm.wjtcm_33_19 · Cited by 30
“For example, a mutation in the H-Ras leads to aberrant functions and is correlated with the development of urinary tract cancer.[75] The correlation between AA exposure and Ras mutation in vivo was initially identified in the 1990s.”
BackgroundGrant, B., Enomoto, M., Ikura, M., & Marshall, C. B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082751 · Cited by 29
“KRAS is of tremendous interest in oncology because KRAS mutations occur in 22% of all tumours, including 61% of pancreas, 33% of colon and 17% of lung cancers [39], 3 of the 5 most lethal cancers world-wide [40].”
BackgroundNovel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
Buday, L., & Vas, V. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09918-2 · Cited by 30
Mutation bias within oncogene families is related to proliferation-specific codon usage
Benisty, H., Weber, M. L., Hernandez‐Alias, X., Schaefer, M. H., & Serrano, L. G. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016119117 · Cited by 30
“These observations suggest that specificities at the level of function and expression might contribute to the RAS mutation patterns observed in human cancers (10).”
BackgroundMechanism of activation and the rewired network: New drug design concepts
Nussinov, R., Zhang, M., Maloney, R., Tsai, C., Yavuz, B. R., Tunçbağ, N., & Jang, H. (2021) · Medicinal Research Reviews · doi:10.1002/med.21863 · Cited by 30
“Cancer drivers often display tissue‐specific mutational frequencies.(308,309) The distinct distributions of Ras isoforms, KRas, NRas, and HRas, and the statistics of their mutations are one example.”
BackgroundHikita, T., Uehara, R., Itoh, R. E., Mitani, F., Miyata, M., Yoshida, T., Yamaguchi, R., & Oneyama, C. (2022) · Cancer Science · doi:10.1111/cas.15288 · Cited by 29
Garcia, B. N. C., van Kempen, L. C. L. T., Kuijpers, C. C. H. J., Schuuring, E. M. D., Willems, S. M., & van der Wekken, A. J. (2022) · Lung Cancer · doi:10.1016/j.lungcan.2022.03.015 · Cited by 30
Chen, J., Zhang, S., Zeng, Q., Wang, W., Zhang, Q., & Liu, X. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.912518 · Cited by 30
“Of the three subfamily members HRAS, KRAS and NRAS, KRAS is the most frequently mutated in cancers (Stephen Andrew et al., 2014; Pylayeva-Gupta et al., 2011).”
BackgroundProgress of small molecules for targeted protein degradation: PROTACs and other technologies
Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31
“2.4.5 | KRAS‐targeting PROTACs KRAS is a GTPase encoded by kirsten rat sarcoma viral oncogene homologue (KRAS) gene which is frequently mutated in cancers (Prior et al., 2012).”
BackgroundInfluentialRamalingam, P. S., Balakrishnan, P., Rajendran, S., Jothi, A., Rajasekaran, R., & Arumugam, S. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45030137 · Cited by 32
“RAS mutations are very co mon, and account for nearly 30% of all cancer types, especially those involved in the aggressive metastatic malignancies of pancreatic (95%), lung (35%), and colorectal (45%) cancers [6].”
BackgroundZheng, Y., Yang, H., Li, T., Zhao, B., Shao, T., Xiang, X., & Cai, W. (2015) · Acta Pharmacologica Sinica · doi:10.1038/aps.2015.4 · Cited by 30
Li, T., Zheng, Y., Sun, H., Zhuang, R., Liu, J., Liu, T., & Cai, W. (2016) · Medical Oncology · doi:10.1007/s12032-016-0777-1 · Cited by 31
“Subtypes of K-Ras mutations occur most frequently at G12D, G12V and G12R [67].”
BackgroundInfluential
Metadata
- Authors
- Prior, I. A., Lewis, P. D., & Mattos, C.
- Affiliations
- Northeastern University (US)
- Corresponding author
- Prior, Ian A.
- Venue
- Cancer Research
- Published
- 2012-05-14
- Volume
- 72
- Issue
- 10
- Pages
- 2457-2467
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3354961
- OpenAlex
- W2135184154
- Cited by
- 2,063
- References
- 67
- Citations by year
- 2026: 114 · 2025: 154 · 2024: 169 · 2023: 203 · 2022: 189 · 2021: 223 · 2020: 203 · 2019: 164 · 2018: 162 · 2017: 144 · 2016: 110 · 2015: 111 · 2014: 52 · 2013: 47 · 2012: 13
- FWCI
- 23.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (067398)
- Cancer Research UK (A6672)
- Biotechnology and Biological Sciences Research Council (BB/G018162/1)
- National Cancer Institute (R56CA096867)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- 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
- Keywords
- RAS mutations, KRAS, H-Ras, NRAS, Ras isoforms, codon 12 mutation, mutational spectra, carcinogenesis, epigenetic mechanisms, Ras signaling
- MeSH terms
- Cell Transformation, Neoplastic, Codon, Humans, Models, Molecular, Molecular Conformation, Neoplasms, Genes, ras, Signal Transduction, Point Mutation, ras Proteins, Protein Isoforms, Catalytic Domain, Databases, Genetic, Epigenesis, Genetic
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