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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 101–200 of 1,006
Bispecific antibodies targeting mutant RAS neoantigens
Douglass, J., Hsiue, E. H.-C., Mog, B. J., Hwang, M. S., DiNapoli, S. R., Pearlman, A. H., Miller, M. S., Wright, K. M., Azurmendi, P. A., Wang, Q., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abd5515 · Cited by 171
“Using MANA-SRM, we detected the G12V[7-16] peptide at 102 copies per cell and the G12V[8-16] peptide at 24 copies per cell in COS-7 cotransfected with HLA-A3 and KRAS G12V (fig.”
BackgroundMethodInfluentialYeganeh, B., Wiecheć, E., Ande, S. R., Sharma, P. K., Moghadam, A. R., Post, M., Freed, D. H., Hashemi, M. M., Shojaei, S., Zeki, A. A., et al. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.02.007 · Cited by 169
Targeting KRAS in metastatic colorectal cancer: current strategies and emerging opportunities
Porru, M., Pompili, L., Caruso, C., Biroccio, A., & Leonetti, C. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0719-1 · Cited by 181
“Mutated KRAS is a major driver for malignant transformation in pancreatic tumors and in lung adenocarcinoma, as G12C mutations are detected in early lesions, retained in all metastases and are a hallmark in the exposure to tobacco smoke, respectively [10].”
BackgroundTargeting epigenetics for cancer therapy
Park, J. W., & Han, J. (2019) · Archives of Pharmacal Research · doi:10.1007/s12272-019-01126-z · Cited by 171
High prevalence of KRAS/BRAF somatic mutations in brain and spinal cord arteriovenous malformations
Hong, T., Yan, Y., Li, J., Radovanovic, I., Ma, X., Shao, Y. W., Yu, J., Ma, Y., Zhang, P., Ling, F., et al. (2018) · Brain · doi:10.1093/brain/awy307 · Cited by 170
“tion of these genes and are all drivers of cancer growth in humans (Cichowski and Janne, 2010; Prior et al., 2012; Simanshu et al., 2017) contrasts with their presence in”
BackgroundEpithelial cell extrusion: Pathways and pathologies
Gudipaty, S. A., & Rosenblatt, J. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.05.010 · Cited by 163
“The vast majority of Rasransformed tumors express a mutated K-Ras isoform, whereas nly 10% of tumors express a mutated H-Ras isoform [34].”
BackgroundThe BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation
Reiff, S. D., Mantel, R., Smith, L. L., Greene, J. T., Muhowski, E. M., Fabian, C. A., Goettl, V. M., Tran, M., Harrington, B. K., Rogers, K. A., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1409 · Cited by 165
Recent advances in chemical protein synthesis: method developments and biological applications
Dong, S., Zheng, J., Li, Y., Wang, H., Chen, G., Chen, Y., Fang, G., Guo, J., He, C., Hu, H., et al. (2024) · Science China Chemistry · doi:10.1007/s11426-024-1950-1 · Cited by 167
Jarvis, I. W. H., Dreij, K., Mattsson, Å., Jernström, B., & Stenius, U. (2014) · Toxicology · doi:10.1016/j.tox.2014.03.012 · Cited by 163
Adjemian, S., Oltean, T., Martens, S., Wiernicki, B., Goossens, V., Berghe, T. V., Cappe, B., Ladik, M., Riquet, F. B., Heyndrickx, L., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03209-y · Cited by 173
Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers
Dillon, M., Lopez, A. R., Lin, E., Sales, D., Perets, R., & Jain, P. (2021) · Cancers · doi:10.3390/cancers13205059 · Cited by 175
MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer
Cui, R., Meng, W., Sun, H., Kim, T., Ye, Z., Fassan, M., Jeon, Y.-J., Li, B., Vicentini, C., Peng, Y., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1502068112 · Cited by 158
“KRAS mutation is frequently seen in lung ADC (42).”
BackgroundKRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge
Mao, Z., Xiao, H., Shen, P., Yang, Y., Xue, J., Yang, Y., Shang, Y., Zhang, L., Li, X., Zhang, Y., et al. (2022) · Cell Discovery · doi:10.1038/s41421-021-00368-w · Cited by 158
Levy-Jurgenson, A., Tekpli, X., Kristensen, V. N., & Yakhini, Z. (2020) · Scientific Reports · doi:10.1038/s41598-020-75708-z · Cited by 155
NRAS mutant melanoma: Towards better therapies
Randic, T., Kozar, I., Margue, C., Utikal, J. S., & Kreis, S. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102238 · Cited by 170
“patients, whereas NRAS mutations are found in ~25% of cases making NRAS the second most frequent mutation type, after BRAF, which affects ~40–45% of all cases [17-20].”
BackgroundThe Functional Proximal Proteome of Oncogenic Ras Includes mTORC2
Kovalski, J. R., Bhaduri, A., Zehnder, A. M., Neela, P. H., Che, Y., Wozniak, G. G., & Khavari, P. A. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.12.001 · Cited by 154
“INTRODUCTION Oncogenic mutations in KRAS, NRAS and HRAS are present in approximately one-third of all human cancers (Prior et al., 2012).”
BackgroundMethodThe role of TBK1 in cancer pathogenesis and anticancer immunity
Runde, A. P., Mack, R. M., Breslin, P., & Zhang, J. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02352-y · Cited by 159
“KRAS is mutated in a wide array of human cancers, including PDA, colorectal, NSCLC, endometrial cancers, and cholangiocarcinoma, most of which are aggressive and resistant to conventional antineoplastic therapies [227, 228].”
BackgroundRare Codons Regulate KRas Oncogenesis
Lampson, B. L., Pershing, N. L., Prinz, J. A., Lacsina, J. R., Marzluff, W. F., Nicchitta, C. V., MacAlpine, D. M., & Counter, C. M. (2012) · Current Biology · doi:10.1016/j.cub.2012.11.031 · Cited by 149
“At face value, the finding that KRAS is an incredibly weak oncogene due to rare codon bias seems at odds with this gene being the most commonly mutated RAS isoform in cancer [34].”
A Small Molecule with Big Impact: MRTX1133 Targets the KRASG12D Mutation in Pancreatic Cancer
Wei, D., Wang, L., Zuo, X., Maitra, A., & Bresalier, R. S. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2098 · Cited by 177
Inhibition of Ras Signaling by Blocking Ras–Effector Interactions with Cyclic Peptides
Upadhyaya, P., Qian, Z., Selner, N. G., Clippinger, S. R., Wu, Z., Briesewitz, R., & Pei, D. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201502763 · Cited by 149
Olea‐Flores, M., Zuñiga‐Eulogio, M. D., Catalán, M. A. M., Rodríguez-Ruiz, H. A., Castañeda-Saucedo, E., Ortuño‐Pineda, C., Padilla‐Benavides, T., & Navarro‐Tito, N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122885 · Cited by 153
“Mutations in codon 12 (H-Ras), 13 (K-Ras), and 61 (N-Ras) are oncogenic as well [141,142].”
BackgroundKey signaling pathways in thyroid cancer
Zaballos, M. A., & Santisteban, P. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0266 · Cited by 153
“Interestingly, each isoform has a distinctive codon mutation signature that is similarly associated with specific tissue and tumor types (Prior et al. 2012).”
Molecular Glue Discovery: Current and Future Approaches
Dewey, J. A., Delalande, C., Azizi, S., Lu, V., Antonopoulos, D. A., & Babnigg, G. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00449 · Cited by 151
Secretome of Intestinal Bacilli: A Natural Guard against Pathologies
Ilinskaya, O. N., Владимировна, У. В., Рашидовна, Я. Д., & Гатауллин, И. Г. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01666 · Cited by 149
“KRAS which has mutations in about 40% of patients with colorectal cancer (Prior et al., 2012) was shown to be a direct target for antitumor binase (Ilinskaya et al., 2016).”
BackgroundMEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma
Yohe, M. E., Gryder, B. E., Shern, J. F., Song, Y., Chou, H.-C., Sindiri, S., Mendoza, A., Patidar, R., Zhang, X., Guha, R., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan4470 · Cited by 147
Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function
Hocker, H. J., Cho, K.-J., Chen, C.-Y. K., Rambahal, N., Sagineedu, S. R., Shaari, K., Stanslas, J., Hancock, J. F., & Gorfe, A. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300016110 · Cited by 144
“Int J Radiat Oncol Biol Phys 77(4):1232–1239.”
BackgroundShin, S., Choi, D.-K., Jung, K., Bae, J., Kim, J., Park, S.-W., Song, K.-H., & Kim, Y. (2017) · Nature Communications · doi:10.1038/ncomms15090 · Cited by 144
Targeting the Small GTPase Superfamily through Their Regulatory Proteins
Gray, J. L., von Delft, F., & Brennan, P. E. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201900585 · Cited by 148
Johnson, C. W., Reid, D., Parker, J. A., Salter, S., Knihtila, R., Kuzmic, P., & Mattos, C. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.778886 · Cited by 133
“It is likely that localization and other large-scale biological contexts play a significant role in the selection of particular mutations in the Ras isoforms associated with specific cancers (76), but it is now clear that conformational states at the active site are affected by sequence at the molecular level in a glo…”
BackgroundSelf-citationCharacteristics of Lung Cancers Harboring NRAS Mutations
Ohashi, K., Sequist, L. V. D., Arcila, M. E., Lovly, C. M., Chen, X., Rudin, C. M., Morán, T., Camidge, D. R., Vnencak‐Jones, C. L., Berry, L. D., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3173 · Cited by 147
BRAF and MEK Inhibitors: Use and Resistance in BRAF-Mutated Cancers
Sanchez, J., Wang, T., & Cohen, M. S. (2018) · Drugs · doi:10.1007/s40265-018-0884-8 · Cited by 148
“As mentioned previously, activating mutations of NRAS contribute to paradoxical MAPK/ERK pathway activation through dimerization of CRAF [2, 3, 6].”
Chen, J., Zhang, S., Wang, W., Pang, L., Zhang, Q., & Liu, X. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01470 · Cited by 140
MEK1/2 Inhibitors: Molecular Activity and Resistance Mechanisms
Wu, P., & Park, J. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.09.023 · Cited by 144
Prakash, P., Zhou, Y., Hong, L., Hancock, J. F., & Gorfe, A. A. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.01.019 · Cited by 135
Aytés, À., Mitrofanova, A., Kinkade, C. W., Lefèbvre, C., Lei, M., Phelan, V., Lekaye, C., Koutcher, J. A., Cardiff, R. D., Califano, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303558110 · Cited by 135
ADAM17 selectively activates the IL‐6 trans‐signaling/ERK MAPK axis in KRAS‐addicted lung cancer
Saad, M. I., Alhayyani, S., McLeod, L., Yu, L., Alanazi, M. A., Deswaerte, V., Tang, K., Jardé, T., Smith, J. A., Prodanovic, Z., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809976 · Cited by 137
“Activating point mutations in KRAS are among the most prevalent genetic alterations in cancer, with highest incidences specific for certain epithelial (e.g., lung, pancreatic, and colorectal) and hematological (e.g., acute myeloid leukemia and multiple myeloma) malignancies (Prior et al, 2012).”
BackgroundExtracellular vesicles and particles impact the systemic landscape of cancer
Lucotti, S., Kenific, C. M., Zhang, H., & Lyden, D. C. (2022) · The EMBO Journal · doi:10.15252/embj.2021109288 · Cited by 145
Zhang, Z., Rohweder, P. J., Ongpipattanakul, C., Basu, K., Bohn, M.-F., Dugan, E. J., Steri, V., Hann, B., Shokat, K. M., & Craik, C. S. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.07.005 · Cited by 136
“ARS1620 modified K-Ras G12C peptides are competent for antigen presentation KRAS G12C is one of the most prevalent oncogenic driver mutations in lung and colon cancer (Prior et al., 2012).”
Takashima, A., & Faller, D. V. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.764990 · Cited by 140
“The catalytic G domain, which is highly homologous among the three isoforms, contains the phosphate-binding loop (P-loop) and two parts of the nucleotide-binding switch regions (Switch I and Switch II) [2].”
BackgroundInfluentialChao, M. P., Gentles, A. J., Chatterjee, S., Lan, F., Reinisch, A., Corces, M. R., Xavy, S., Shen, J., Haag, D., Chanda, S., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2016.11.018 · Cited by 141
“AML-iPSCs from both cases possessed mutations known to be oncogenic drivers in multiple cancer types, including CNS tumors, such as MLL, ARID1A, ATM, and RAS (Choi et al., 2016; Knobbe et al., 2004; Parsons et al., 2011; Prior et al., 2012; Sausen et al., 2013).”
Cruz-Migoni, A., Canning, P., Quevedo, C. E., Bataille, C. J. R., Béry, N., Miller, A., Russell, A. J., Phillips, S. E. V., Carr, S. B., & Rabbitts, T. H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811360116 · Cited by 135
“Mutations reduce GAP activity leading to constitutive activation of RAS effector pathways (2), constantly generating a signaling cascade that activates cell functions such as division, survival, and invasion (9).”
Deconstruction of the Ras switching cycle through saturation mutagenesis
Bandaru, P., Shah, N. H., Bhattacharyya, M., Barton, J. P., Kondo, Y., Cofsky, J. C., Gee, C. L., Chakraborty, A. K., Kortemme, T., Ranganathan, R., et al. (2017) · eLife · doi:10.7554/elife.27810 · Cited by 117
“Given that protein structures are tolerant to mutation, why are the sequences of Ras proteins (referred to collectively as ‘Ras’) so highly conserved? In particular, to what extent does the high degree of sequence conservation arise from the necessity to maintain the GTPase cycle that switches signaling on and off? Th…”
BackgroundInfluentialSignal Integration by Lipid-Mediated Spatial Cross Talk between Ras Nanoclusters
Zhou, Y., Hong, L., Rodkey, T. L., Ariotti, N., Parton, R. G., & Hancock, J. F. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01227-13 · Cited by 133
“Oncogenic mutations in H-Ras are extremely rare in human tumors (60); it is tempting to speculate that the quenching of K-Ras signaling that results from H-Ras–GTP expression may be of relevance.”
BackgroundKRAS Mutations as Prognostic and Predictive Markers in Non–Small Cell Lung Cancer
Martin, P., Leighl, N. B., Tsao, M., & Shepherd, F. A. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318283d958 · Cited by 135
“KRAS is mutated in approximately 22% of all tumors.(18) RAS proteins function as binary switches of guanosine diphosphate (GDP)/guanosine triphosphate (GTP) (Fig.”
BackgroundQuevedo, C. E., Cruz-Migoni, A., Béry, N., Miller, A., Tanaka, T. U., Petch, D., Bataille, C. J. R., Lee, L. Y. W., Fallon, P. S., Tulmin, H., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05707-2 · Cited by 134
Nussinov, R., Jang, H., Tsai, C., & Cheng, F. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006658 · Cited by 134
Past, Present and Future of Oncolytic Reovirus
Müller, L. M. E., Berkeley, R. A., Barr, T., Ilett, E. J., & Errington‐Mais, F. (2020) · Cancers · doi:10.3390/cancers12113219 · Cited by 130
“RAS mutations are prevalent in cancer [61], supporting the use of reovirus as a potential therapeutic agent [58,62].”
Background10 Years Into the Resurgence of Covalent Drugs
Vita, E. D. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0236 · Cited by 125
“KRASG12C is the most common RAS mutant in lung cancer [56].”
BackgroundAlveolar progenitor cells and the origin of lung cancer
de Aja, J. S., Dost, A. F. M., & Kim, C. F. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13201 · Cited by 136
Metastatic Melanoma: Insights Into the Evolution of the Treatments and Future Challenges
Millet, A., Martin, A. R., Ronco, C., Rocchi, S., & Benhida, R. (2016) · Medicinal Research Reviews · doi:10.1002/med.21404 · Cited by 135
Targeting PP2A in cancer: Combination therapies
Mazhar, S., Taylor, S. E., Sangodkar, J., & Narla, G. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.08.020 · Cited by 130
“at the G12 residue [48], resulting in hyperactive signaling to growth and survival pathways, including the mitogen activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) pathways [49].”
BackgroundGlycogen Synthase Kinase 3β in Cancer Biology and Treatment
Domoto, T., Uehara, M., Bolidong, D., & Minamoto, T. (2020) · Cells · doi:10.3390/cells9061388 · Cited by 134
Nonhistone Lysine Methylation in the Regulation of Cancer PathwaysPreprint
Carlson, S. M., & Gozani, O. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026435 · Cited by 133
“The link to K-Ras is clinically important because mutations in the K-Ras gene occur in more than half of all human cancers (Forrester et al. 1987; Prior et al. 2012).”
BackgroundShepherd, F. A., Lacas, B., Le Teuff, G., Hainaut, P., Jänne, P. A., Pignon, J.-P., Le Chevalier, T., Seymour, L., Douillard, J.-Y., Graziano, S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.2893 · Cited by 124
GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf
Zhang, Z., Gao, R., Hu, Q., Peacock, H., Peacock, D. M., Dai, S., Shokat, K. M., & Suga, H. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00514 · Cited by 124
Oncogenic Ras Isoforms Signaling Specificity at the Membrane
Nussinov, R., Tsai, C., & Jang, H. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-2727 · Cited by 124
Navigating the ERK1/2 MAPK Cascade
Martín-Vega, A., & Cobb, M. H. (2023) · Biomolecules · doi:10.3390/biom13101555 · Cited by 127
KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing
Lim, T. K. H., Skoulidis, F., Kerr, K. M., Ahn, M., Kapp, J. R., Soares, F. A., & Yatabe, Y. (2023) · Lung Cancer · doi:10.1016/j.lungcan.2023.107293 · Cited by 133
A new genomic framework to categorize pediatric acute myeloid leukemia
Umeda, M., Ma, J., Westover, T., Ni, Y., Song, G., Maciaszek, J. L., Rusch, M., Rahbarinia, D., Foy, S. G., Huang, B. J., et al. (2024) · Nature Genetics · doi:10.1038/s41588-023-01640-3 · Cited by 126
“It is well-established that each RAS mutation has preferential distribution among cancer subtypes 53 .”
BackgroundTrinh, T. B., Upadhyaya, P., Qian, Z., & Pei, D. (2015) · ACS Combinatorial Science · doi:10.1021/acscombsci.5b00164 · Cited by 119
Strategies for designing proteolysis targeting chimaeras (PROTACs)
He, S., Dong, G., Cheng, J., Wu, Y., & Sheng, C. (2022) · Medicinal Research Reviews · doi:10.1002/med.21877 · Cited by 120
“Mutational activation of KRAS is a common feature accounting for approximately 20% of human cancers.(208) G12C‐”
BackgroundInflammation and cancer: Till death tears them apart
Raposo, T. P., Beirão, B. C. B., Pang, L. Y., QUEIROGA, F. L., & Argyle, D. J. (2015) · The Veterinary Journal · doi:10.1016/j.tvjl.2015.04.015 · Cited by 121
“…increased size of tumour (Keniry and Parsons, 2008) RAS Protein superfamily of small GTPases Regulates pathways important for cell survival and proliferation (Prior et al., 2012) ROS Reactive oxygen species Reaction to stressors affecting inflammation; cell transformation (Gupta et al., 2012)…”
Discovery of hidden allosteric sites as novel targets for allosteric drug design
Lu, S., Ji, M., Ni, D., & Zhang, J. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.10.001 · Cited by 119
Jerchel, I. S., Hoogkamer, A. Q., Ariës, I. M., Steeghs, E. M. P., Boer, J. M., Besselink, N. J. M., Boeree, A., van de Ven, C., de Groot‐Kruseman, H. A., de Haas, V., et al. (2017) · Leukemia · doi:10.1038/leu.2017.303 · Cited by 117
Montor, W. R., Salas, A. R. O. S. E., & de Melo, F. H. M. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0792-2 · Cited by 118
“However, in breast, melanoma, brain and ovarian tumors, these mutations are less common [54, 55].”
BackgroundEmmanuel, C., Chiew, Y., George, J., Etemadmoghadam, D., Anglesio, M., Sharma, R. N., Russell, P., Kennedy, C., Fereday, S., Hung, J., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1292 · Cited by 102
“Indeed, NRAS is a recognized oncogene in other cancer types, including leukemia and melanoma (46, 47), and mutant NRAS was identified in an in vitro retroviral expression library screen for ovarian oncogenes (48).”
BackgroundTerrell, E. M., Durrant, D., Ritt, D. A., Sealover, N. E., Sheffels, E., Spencer-Smith, R., Esposito, D., Zhou, Y., Hancock, J. F., Kortum, R. L., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.004 · Cited by 110
“Importantly, disease-associated mutations tend to render Ras insensitive to GAP stimulation and reduce its intrinsic GTPase activity, leaving Ras in a constitutively active state that promotes pathway activation in an unregulated manner (Prior et al., 2012).”
BackgroundLiquid Biopsy, ctDNA Diagnosis through NGS
Chen, L., Liu, X., Zheng, B., Ke, R., & Tzeng, C. (2021) · Life · doi:10.3390/life11090890 · Cited by 117
“KRAS G12R Biomarker of tumor evolution and prognostic impact [70]”
BackgroundCho, K.-J., van der Hoeven, D., Zhou, Y., Maekawa, M., Ma, X., Chen, W., Fairn, G. D., & Hancock, J. F. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00719-15 · Cited by 112
“Of the three ubiquitously expressed Ras isoforms, H-, N-, and K-Ras, oncogenic mutant K-Ras is the most prevalent, being expressed in 95% of pancreatic, 45% of colorectal, and 35% of lung cancers (1).”
BackgroundOncogene-induced senescence: From biology to therapy
Zhu, H., Blake, S., Kusuma, F. K., Pearson, R. B., Kang, J., & Chan, K. T. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111229 · Cited by 116
Ni, D., Lu, S., & Zhang, J. (2019) · Medicinal Research Reviews · doi:10.1002/med.21585 · Cited by 116
“Mutations of Ras are observed in approximately 30% of human cancers.(127) Ras functions through associations with numerous effector proteins,(128) such as Raf kinase, son of sevenless (SOS), phosphatidylinositol 3‐kinase (PI3K), and Ral guanine nucleotide dissociation stimulator (RalGDS).”
BackgroundTherapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen
Poole, A. J., Karuppiah, V., Hartt, A., Haidar, J. N. S., Moureau, S., Dobrzycki, T., Hayes, C., Rowley, C. N., Dias, J. C., Harper, S. J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32811-1 · Cited by 115
Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission
van der Hoeven, D., Cho, K.-J., Ma, X., Chigurupati, S., Parton, R. G., & Hancock, J. F. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00884-12 · Cited by 113
The Calcium-Signaling Toolkit in Cancer: Remodeling and TargetingPreprint
Roberts‐Thomson, S. J., Chalmers, S. B., & Monteith, G. R. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035204 · Cited by 112
“The RAS family of genes are proto-oncogenes that are frequently mutated in human cancers (Prior et al. 2012).”
BackgroundRAS proto-oncogene in medullary thyroid carcinoma
Moura, M. M., Cavaco, B. M., & Leite, V. A. P. H. (2015) · Endocrine Related Cancer · doi:10.1530/erc-15-0070 · Cited by 111
“However, these values are biased, because colorectal cancer, where KRAS mutations predominate, represents most of the cases (Prior et al. 2012).”
BackgroundOikonomou, E., Koustas, E., Goulielmaki, M., & Pintzas, A. (2014) · Oncotarget · doi:10.18632/oncotarget.2555 · Cited by 113
“com/oncotarget common abnormality of dominant oncogenes in human tumours [21] and is a common event in the development and progression of adenocarcinomas of the pancreas (90%), colon (50%), thyroid (50%), bladder (50%), and lung (30%).”
BackgroundRAF suppression synergizes with MEK inhibition in KRAS mutant cancer cells
Lamba, S., Russo, M., Sun, C., Lazzari, L., Cancelliere, C., Grernrum, W., Lieftink, C., Bernards, R., Di Nicolantonio, F., & Bardelli, A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.033 · Cited by 110
“Mutations in the gene encoding the guanosine triphosphatase protein KRAS, the principal of the three isoforms of RAS, are present in approximately 20% of all cancers and are associated with poor prognosis and resistance to therapy (Prior et al., 2012; Pylayeva-Gupta et al., 2011).”
Molecular Spies in Action: Genetically Encoded Fluorescent Biosensors Light up Cellular Signals
Gest, A. M. M., Sahan, A. Z., Zhong, Y., Lin, W., Mehta, S., & Zhang, J. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00293 · Cited by 112
Best, S. A., Ding, S., Kersbergen, A., Dong, X., Song, J.-Y., Xie, Y., Reljic, B., Li, K., Vince, J. E., Rathi, V., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12164-y · Cited by 108
Urano, M., Nakaguro, M., Yamamoto, Y., Hirai, H., Tanigawa, M., Saigusa, N., Shimizu, A., Tsukahara, K., Tada, Y., Sakurai, K., et al. (2019) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001258 · Cited by 108
K-Ras protein as a drug target
McCormick, F. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1382-7 · Cited by 105
“Activating mutations of signaling molecules occur in many types of cancer, often at high frequencies [1].”
BackgroundSchmick, M., Kraemer, A., & Bastiaens, P. I. H. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.02.004 · Cited by 110
Ras signaling through RASSF proteins
Donninger, H., Schmidt, M., Mezzanotte-Sharpe, J., Barnoud, T., & Clark, G. J. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.06.007 · Cited by 110
Targeting KRAS in pancreatic cancer: new drugs on the horizon
Bannoura, S. F., Uddin, M. H., Nagasaka, M., Fazili, F., Hallak, M. N. A., Philip, P. A., El‐Rayes, B. F., & Azmi, A. S. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09990-2 · Cited by 112
Dey, A., Mitra, A., Pathak, S., Prasad, S. V., Sun-Zhang, A., Zhang, H., Sun, X., & Banerjee, A. (2023) · Technology in Cancer Research & Treatment · doi:10.1177/15330338231178403 · Cited by 108
“Three forms of RAS proteins are expressed: Harvey Ras (H-Ras), Kirsten Ras (K-Ras), and neuroblastoma Ras (N-Ras).(75) KRAS is the gene that expresses the K-Ras protein.”
BackgroundOncogenic KRAS: Signaling and Drug Resistance
Kim, H. J., Lee, H. N., Jeong, M. S., & Jang, S. B. (2021) · Cancers · doi:10.3390/cancers13225599 · Cited by 105
“The most mutation sites of oncogenic mutation in RAS are residues 12 and 13 in the P-loop, and residue 61 in switch II [72].”
BackgroundKRAS G12C–Mutant Non–Small Cell Lung Cancer
Veluswamy, R., Mack, P. C., Houldsworth, J., Elkhouly, E., & Hirsch, F. R. (2021) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.02.002 · Cited by 96
Protein ensembles link genotype to phenotype
Nussinov, R., Tsai, C., & Jang, H. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006648 · Cited by 102
The impact of oncogenic RAS on redox balance and implications for cancer development
Lim, J. K. M., & Leprivier, G. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2192-y · Cited by 106
Lipoproteins and cancer: The role of HDL-C, LDL-C, and cholesterol-lowering drugs
Patel, K. K., & Kashfi, K. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114654 · Cited by 105
Site-specific monoubiquitination activates Ras by impeding GTPase-activating protein function
Baker, R., Lewis, S. M., Sasaki, A. T., Wilkerson, E., Locasale, J. W., Cantley, L. C., Kuhlman, B. A., Dohlman, H. G., & Campbell, S. L. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2430 · Cited by 101
Olson, M. F. (2016) · Small GTPases · doi:10.1080/21541248.2016.1218407 · Cited by 103
“quencies of activating mutations in human cancers that work by reducing intrinsic and/or GAP-induced GTPase activity, thereby locking the protein in the on-state.(51) Similar GTPase deficient mutations have not been”
BackgroundSmall-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics
Chen, H., Smaill, J. B., Liu, T., Ding, K., & Lu, X. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01312 · Cited by 104
Ferreira, A. I., Pereira, F. D. S., Reis, C. A., Oliveira, M. J., Sousa, M. J., & Preto, A. (2022) · Cells · doi:10.3390/cells11142183 · Cited by 111
“Therefore, their specific roles may be explained by various others factors, such as cellular context, differential interaction with effectors, compartmentalized signaling and PTMs [14].”
BackgroundSrc promotes GTPase activity of Ras via tyrosine 32 phosphorylation
Bunda, S., Heir, P., Srikumar, T., Cook, J. D., Burrell, K. E., Kano, Y., Lee, J. E., Zadeh, G. M., Raught, B., & Ohh, M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1406559111 · Cited by 102
“A previous study has shown that the aberrant positioning of Y32 in oncogenic Ras prohibited efficient GTP hydrolysis (54).”
BackgroundTolcher, A. W., Peng, W., & Calvo, E. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0349 · Cited by 101
Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC
Yang, F., Wen, Y., Wang, C., Zhou, Y., Zhou, Y., Zhang, Z.-M., Liu, T., & Lu, X. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.114088 · Cited by 109
Molecular genetics and cellular events of K-Ras-driven tumorigenesis
Jinesh, G. G., Sambandam, V., Vijayaraghavan, S., Balaji, K., & Mukherjee, S. (2017) · Oncogene · doi:10.1038/onc.2017.377 · Cited by 100
Expanding the scope of electrophiles capable of targeting K-Ras oncogenes
McGregor, L. M., Jenkins, M. L., Kerwin, C., Burke, J. E., & Shokat, K. M. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00271 · Cited by 97
DriverDBv2: a database for human cancer driver gene research
Chung, I., Chen, C., Su, S.-C., Li, C., Wu, K., Wang, H., & Cheng, W. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1314 · Cited by 97
“Many driver mutations recurrently occur in the functional regions of proteins (for example, kinase domains or binding domains) (6) or interrupt active sites (for example, phosphorylation sites) (7).”
Background
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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