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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 801–900 of 1,006
Ras suppression potentiates rear actomyosin contractility-driven cell polarization and migration
Lin, Y., Pal, D. S., Banerjee, P., Banerjee, T., Qin, G., Deng, Y., Borleis, J. A., Iglesias, P. A., & Devreotes, P. N. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01453-4 · Cited by 26
Identification of a ternary protein-complex as a therapeutic target for K-Ras-dependent colon cancer
Qi, X.-M., Xie, C., Hou, S., Li, G., Yin, N. B., Dong, L., Lepp, A., Chesnik, M. A., Mirza, S. P., Szabó, A., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2001 · Cited by 25
Kopra, K., Ligabue, A., Wang, Q., Syrjänpää, M., Blaževitš, O., Veltel, S., van Adrichem, A. J., Hanninen, P. E., Abankwa, D., & Härmä, H. (2014) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-014-7795-7 · Cited by 24
“Mutations in Ras are frequent and can be found in approximately 30 % of human cancers and in several developmental disorders [6, 7].”
BackgroundRapalogs can promote cancer cell stemness in vitro in a Galectin-1 and H-ras-dependent manner
Posada, I. M. D., Lectez, B. L. P., Sharma, M., Oetken-Lindholm, C., Yetukuri, L., Zhou, Y., Aittokallio, T. A., & Abankwa, D. (2017) · Oncotarget · doi:10.18632/oncotarget.17819 · Cited by 24
“Hotspot mutations in codon 12, 13 and 61 render Ras constitutively active and make it a major driver in cancer [11].”
BackgroundDirect physical interaction of active Ras with mSIN1 regulates mTORC2 signaling
Lone, M. D., Miyan, J., Asif, M., Malik, S. A., Dubey, P., Singh, V., Singh, K., Mitra, K., Pandey, D., Haq, W., et al. (2019) · BMC Cancer · doi:10.1186/s12885-019-6422-6 · Cited by 25
Exploiting RAS Nucleotide Cycling as a Strategy for Drugging RAS-Driven Cancers
Mattox, T. E., Chen, X., Maxuitenko, Y. Y., Keeton, A. B., & Piazza, G. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010141 · Cited by 25
“Mutations in RAS genes are also known to cause developmental disorders of the heart and nervous system, known as RASopathies [1].”
BackgroundInfluentialWang, S., Cheng, L., Wu, H., & Li, G. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.949656 · Cited by 25
“RAS family is one of the most frequently mutated families in CRC (67).”
BackgroundDynamic conformational equilibria in the active states of KRAS and NRAS
Rennella, E., Henry, C., Dickson, C. J., Georgescauld, F., Wales, T. E., Erdmann, D., Cotesta, S., Maira, S.-M., Sedrani, R. C., Brachmann, S. M., et al. (2024) · RSC Chemical Biology · doi:10.1039/d4cb00233d · Cited by 24
D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial
Cho, B. C., Lü, S., Lee, M. A., Song, Z., Park, J., Lim, S. M., Li, Z., Zhao, J., Richardson, G. E., Zhang, Y., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03688-6 · Cited by 24
Wang, J., Wang, W., Li, J., Wu, L., Song, M. L., & Meng, Q. (2017) · OncoTargets and Therapy · doi:10.2147/ott.s121864 · Cited by 24
Flux: Overcoming Scheduling Challenges for Exascale Workflows
Ahn, D. H., Bass, N., Chu, A., Garlick, J. E., Grondona, M., Herbein, S., Koning, J. M., Patki, T., Scogland, T., Springmeyer, B., et al. (2018) · doi:10.1109/works.2018.00007 · Cited by 24
“It was discovered over forty years ago that 30% of human cancers are caused by the RAS family of cancer-causing genes [12].”
BackgroundKrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice
Wong, J. C. Y., Pérez-Mancera, P. A., Huang, T. Q., Kim, J., Grego‐Bessa, J., Alzamora, M. D. P., Kogan, S. C., Sharir, A., Keefe, S. H., Morales, C. E., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.140495 · Cited by 24
“reduced rates of intrinsic GTP hydrolysis and resistance to GTPase-activating proteins (GAPs) (5).”
BackgroundSynergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS‐mutant cancer
Zhang, Y., Liang, S., Saliakoura, M., Yang, H., Vassella, E., Konstantinidou, G., Tschan, M. P., Hegedűs, B., Zhao, L., Gao, Y., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013193 · Cited by 23
“More than 30% of non-small cell lung cancer (NSCLC) patients have KRAS mutations (Prior et al , 2012; Barlesi et al , 2016).”
Wang, X. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c00844 · Cited by 23
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 · doi:10.1002/ange.201502763 · Cited by 24
Emerging roles of hnRNP A2B1 in cancer and inflammation
Xu, H., Li, P., Wang, X., Zhuang, H., & Hua, Z. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.09.104 · Cited by 27
Mouse models of Kras activation in gastric cancer
Won, Y., & Choi, E.-Y. K. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00882-1 · Cited by 23
Proulx-Rocray, F., Routy, B., Nassabein, R. M., Belkaïd, W., Tran‐Thanh, D., Malo, J., Tonneau, M., Ouarzadi, O. E., Florescu, M., Tehfe, M. A., et al. (2023) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2023.100767 · Cited by 29
Targeting KRAS Diversity: Covalent Modulation of G12X and Beyond in Cancer Therapy
Kirschner, T., Müller, M. P., & Rauh, D. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c02403 · Cited by 23
Identification and affinity enhancement of T-cell receptor targeting a KRASG12V cancer neoantigen
Zhang, M., Xu, W. L., Luo, L., Guan, F., Wang, X., Zhu, P., Zhang, J., Zhou, X., Wang, F., & Ye, S. (2024) · Communications Biology · doi:10.1038/s42003-024-06209-2 · Cited by 24
“Speci fi cally, Gly12 point mutations in KRAS are highly prevalent, accounting for ~80% of KRAS-mutated malignancies, with 41% being G12D, 28% G12V, and 14% G12C 49,50 .”
SPRED1 Interferes with K-ras but Not H-ras Membrane Anchorage and Signaling
Siljamäki, E., & Abankwa, D. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00191-16 · Cited by 24
“KRAS is the most frequently mutated isoform, with oncogenic mutations detected in 22% of all screened tumors, while the rates for mutations in HRAS and NRAS are lower (8% and 3%, respectively) (19, 20).”
BackgroundMitochondrial mutations in human cancer: Curation of translation
Caudron‐Herger, M., & Diederichs, S. (2017) · RNA Biology · doi:10.1080/15476286.2017.1373239 · Cited by 24
“This control layer is essential and extremely important as COSMIC is the leading source of information for many studies [10-12].”
BackgroundRAS Regulates the Transition from Naive to Primed Pluripotent Stem Cells
Altshuler, A., Verbuk, M., Bhattacharya, S., Abramovich, I., Haklai, R., Hanna, J. H., Kloog, Y., Gottlieb, E., & Shalom‐Feuerstein, R. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.01.004 · Cited by 24
Saida, K., Murase, T., Ito, M., Fujii, K., Takino, H., Masaki, A., Kawakita, D., Ijichi, K., Tada, Y., Kusafuka, K., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24818 · Cited by 25
“These proteins are GTPases that may function as a molecular switch regulating the EGFR pathways responsible for proliferation and cell survival [12].”
BackgroundLai, H., Wang, Y., Duan, F., Li, Y., Jiang, Z., Luo, L., Liu, L., Leung, E. L., & Yao, X. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00958 · Cited by 24
Grigorenko, B. L., Kots, E. D., & Nemukhin, A. V. (2019) · Organic & Biomolecular Chemistry · doi:10.1039/c9ob00463g · Cited by 24
Pan-Cancer and Single-Cell Modeling of Genomic Alterations Through Gene Expression
Mercatelli, D., Ray, F., & Giorgi, F. M. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00671 · Cited by 23
“Our results confirm the key role of KRAS-targeting somatic mutations, which are well modeled by gene expression in KRAS-driven tumors: colon, lung, pancreas, stomach, and testicular cancers, as well as cervical squamous carcinoma (Prior et al., 2012) ( Figure 3 ).”
ResultMouse models of thyroid cancer: Bridging pathogenesis and novel therapeutics
Jin, Y., Liu, M., Sa, R., Fu, H., Cheng, L., & Chen, L. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.09.017 · Cited by 24
Saha, G., Singh, R., Mandal, A., Das, S. K., Chattopadhyay, E., Panja, P., Roy, P., Sarkar, N. D., Gulati, S., Ghatak, S., et al. (2020) · Molecular Medicine · doi:10.1186/s10020-020-00183-1 · Cited by 23
Drug screening strategies using metal-based luminescent probes
Li, G., Chun, W., Ma, D., & Leung, C. (2021) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2021.116270 · Cited by 24
Fonseca, I., Bell, A., Wani, K., & Bell, D. (2014) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22238 · Cited by 23
“In contrast, the molecular profile of EMC has not been well studied, although an association with Harvey rat sarcoma viral oncogene homolog (HRAS) mutations has been noted in recent studies (Prior et al. 2012; Cros et al. 2013; Chiosea et al. 2014).”
RBEL1 is required for osteosarcoma cell proliferation via inhibiting retinoblastoma 1
TANG, H., Ji, F., Sun, J., Xie, Y., Xu, Y.-Y., & Yue, H.-T. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4670 · Cited by 23
“One function of Rb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide (11,30).”
Functional characterisation of a novel class of in-frame insertion variants of KRAS and HRAS
Eijkelenboom, A., van Schaik, F. M. A., van Es, R. M., Broek, R. W. T., Rinne, T., van der Vleuten, C., Flucke, U. E., Ligtenberg, M. J. L., & Rehmann, H. (2019) · Scientific Reports · doi:10.1038/s41598-019-44584-7 · Cited by 23
How Anionic Lipids Affect Spatiotemporal Properties of KRAS4B on Model Membranes
Ngo, V. A., Sarkar, S., Neale, C., & Garcı́a, A. E. (2020) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.0c02642 · Cited by 22
Poulsen, T. S., de Oliveira, D. V. N. P., Espersen, M. L. M., Klarskov, L. L., Skovrider‐Ruminski, W., & Høgdall, E. V. S. (2020) · Apmis · doi:10.1111/apm.13091 · Cited by 23
“sites such as codons 12, 13 and 61 typically cause impairment of GTP hydrolysis leading to constitutive activation of the RAS pathway (35).”
BackgroundCa2+ Signaling and Its Potential Targeting in Pancreatic Ductal Carcinoma
Bettaieb, L., Brulé, M., Chomy, A., Diedro, M., Fruit, M., Happernegg, E., Heni, L., Horochowska, A., Housseini, M., Klouyovo, K., et al. (2021) · Cancers · doi:10.3390/cancers13123085 · Cited by 24
“Recent studies highlight that the Ca2+/CaM complex controls the KRas4B pathway due to the KRAS mutation present in 90% of human PDAC cases [48].”
BackgroundNussinov, R., Tsai, C., & Jang, H. (2021) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2021.05.009 · Cited by 24
Targeting RAS in neuroblastoma: Is it possible?
Lin, L., Miao, L., Lin, H., Cheng, J., Li, M., Zhuo, Z., & He, J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108054 · Cited by 24
LRRK2 dynamics analysis identifies allosteric control of the crosstalk between its catalytic domains
Weng, J., Aoto, P. C., Lorenz, R., Wu, J., Schmidt, S. H., Manschwetus, J. T., Sharma, P. K., Silletti, S., Mathea, S., Chatterjee, D., et al. (2022) · PLoS Biology · doi:10.1371/journal.pbio.3001427 · Cited by 25
“Whether this is physiologically important remains to be established; however, T1343 is homologs G12 in RAS and is common disease mutation [32,33].”
Structural determinants of REMORIN nanodomain formation in anionic membranes
Legrand, A., Cava, D. G., Jolivet, M.-D., Décossas, M., Lambert, O., Bayle, V., Jaillais, Y., Loquet, A., Germain, V., Boudsocq, M., et al. (2022) · Biophysical Journal · doi:10.1016/j.bpj.2022.12.035 · Cited by 23
Salivary gland carcinoma: Towards a more personalised approach
Rached, L., Saleh, K., Casiraghi, O., & Even, C. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102697 · Cited by 25
Rat Models of Hormone Receptor-Positive Breast Cancer
Nicotra, R., Lutz, C., Messal, H. A., & Jonkers, J. (2024) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-024-09566-0 · Cited by 30
“Since HRAS mutations are not frequently detected in human BCs, with rates as low as 1%, DMBA-induced rat tumors could thus be a better representation of the human disease [156, 157].”
BackgroundKopra, K., & Härmä, H. (2015) · New Biotechnology · doi:10.1016/j.nbt.2015.02.007 · Cited by 25
Quah, S. Y., Tan, M. S., Teh, Y. H., & Stanslas, J. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.010 · Cited by 26
Tan, L., Cho, K.-J., Neupane, P., Capon, R. J., & Hancock, J. F. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003907 · Cited by 22
“Oncogenic mutations that lock RAS in the GTP-bound state occur in 15% of all human cancers, leading to constitutive activation of downstream effectors (1, 2).”
BackgroundAcylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function
Tan, L., Cho, K., Kattan, W. E., Garrido, C. M., Zhou, Y., Neupane, P., Capon, R. J., & Hancock, J. F. (2019) · Journal of Cell Science · doi:10.1242/jcs.232132 · Cited by 23
“KRAS mutations are the most prevalent, accounting for ∼85% of all RAS mutations reported (Prior et al., 2012).”
BackgroundZhang, Y., Meng, X., Tang, H., Cheng, M., Yang, F., & Xu, W. (2019) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2019.1702653 · Cited by 23
Ras isoforms: signaling specificities in CD40 pathway
Nair, A., Chakraborty, S., Banerji, L. A., Srivastava, A., Navare, C., & Saha, B. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-019-0497-1 · Cited by 23
Creeden, J. F., Alganem, K., Imami, A. S., Henkel, N., Brunicardi, F. C., Liu, S., Shukla, R., Tomar, T., Naji, F., & McCullumsmith, R. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228823 · Cited by 22
“PDAC presents with approximately 90% KRAS mutation frequency [204].”
BackgroundRuan, D.-Y., Wu, H.-X., Xu, Y., Munster, P. N., Deng, Y., Richardson, G., Yan, D., Lee, M.-A., Lee, K.-W., Pan, H., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02274-z · Cited by 22
KRAS mutation-driven angiopoietin 2 bestows anti-VEGF resistance in epithelial carcinomas
Hosaka, K., Andersson, P., Wu, J., He, X., Du, Q., Xu, J., Seki, T., Gao, J., Zhang, Y., Sun, X., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2303740120 · Cited by 22
“RAS proteins belong to protooncogenes that are frequently mutated in most common human cancers, including epithelial cell–derived cancer types such as pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) (13–15).”
Clinical advances and challenges associated with TCR-T cell therapy for cancer treatment
Li, J., Zhang, Y., Fu, T., Xing, G., Cai, H., Li, K., Xu, Y., & Tong, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1487782 · Cited by 22
“KRAS mutations represent a critical area of focus because they are frequently associated with tumor proliferation and survival (35).”
BackgroundRAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis
Nászai, M., Bellec, K., Yu, Y., Román‐Fernández, Á., Sandilands, E., Johansson, J., Campbell, A. D., Norman, J. C., Sansom, O. J., Bryant, D. M., et al. (2021) · eLife · doi:10.7554/elife.63807 · Cited by 20
Ros, J., Baraibar, I., Martini, G., Salvà, F., Gonzalez, N. S., Cuadra‐Urteaga, J. L., Dienstmann, R., Tabernero, J. M., & Élez, E. (2021) · Current Treatment Options in Oncology · doi:10.1007/s11864-021-00913-5 · Cited by 22
Targeting Oncogenic KRAS in Non-Small-Cell Lung Cancer
Sunaga, N., Miura, Y., Kasahara, N., & Sakurai, R. (2021) · Cancers · doi:10.3390/cancers13235956 · Cited by 23
“KRAS mutations are commonly detected in pancreatic cancer, colorectal cancer and NSCLC [20,21].”
BackgroundHow Phosphofructokinase-1 Promotes PI3K and YAP/TAZ in Cancer: Therapeutic Perspectives
Simula, L., Alifano, M., & Icard, P. (2022) · Cancers · doi:10.3390/cancers14102478 · Cited by 22
“(i) gain function mutations, in particular of PI3K or membrane receptors, such as receptor tyrosine kinases (RTKs), promoting PI3K activity [2,14]; (ii) compensatory activation of pathways able to bypass the PI3K inhibition, such as the activation of JAK2/STAT5 [15] and/or insulin dependent pathways (promoted by insul…”
Zhuang, H., Fan, J., Li, M., Zhang, H., Yang, X., Lin, L., Lu, S., Wang, Q., & Liu, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.915512 · Cited by 23
“Accumulating evidence indicates that oncogenic RAS mutations participate in approximately 30% of human cancers and induce over 1 million deaths per year worldwide (6, 7).”
BackgroundDirect GDP-KRAS G12C inhibitors and mechanisms of resistance: the tip of the iceberg
Rosen, J. C., Sacher, A. G., & Tsao, M. (2023) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359231160141 · Cited by 22
Origin and Evolution of RAS Membrane Targeting
García‐España, A., & Philips, M. R. (2023) · Oncogene · doi:10.1038/s41388-023-02672-z · Cited by 23
“Oncogenic mutations in their catalytic domains, particularly at residues G12, G13, and Q61, are among the most common in human tumors [3].”
BackgroundPersonalized Treatment for Patients With Colorectal Cancer: Role of Biomarkers
Duffy, M. J. (2015) · Biomarkers in Medicine · doi:10.2217/bmm.15.3 · Cited by 23
The Ras Superfamily G-Proteins
Tetlow, A. L., & Tamanoi, F. (2013) · The Enzymes · doi:10.1016/b978-0-12-416749-0.00001-4 · Cited by 22
Development of Substrate‐Derived Sirtuin Inhibitors with Potential Anticancer Activity
Kuhlmann, N., Chollet, C., Baldus, L., Neundorf, I., & Lammers, M. (2017) · ChemMedChem · doi:10.1002/cmdc.201700414 · Cited by 22
Methionine 170 is an Environmentally Sensitive Membrane Anchor in the Disordered HVR of K-Ras4B
Neale, C., & Garcı́a, A. E. (2018) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.8b07919 · Cited by 20
Yu, Z., Chen, Z., Su, Q., Ye, S., Yuan, H., Kuai, M., Lv, M., Tu, Z., Yang, X., Liu, R., et al. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.01.028 · Cited by 22
Small Molecule SOS1 Agonists Modulate MAPK and PI3K Signaling via Independent Cellular Responses
Akan, D. T., Howes, J. E., Sai, J., Arnold, A. L., Beesetty, Y., Phan, J., Olejniczak, E. T., Waterson, A. G., & Fesik, S. W. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b00869 · Cited by 22
Hair follicle regeneration suppresses Ras-driven oncogenic growth
Pineda, C. M., Gonzalez, D. G., Matte-Martone, C. C., Boucher, J. D., Lathrop, E., Gallini, S., Fons, N. R., Xin, T., Tai, K., Marsh, E. D., et al. (2019) · The Journal of Cell Biology · doi:10.1083/jcb.201907178 · Cited by 20
“For instance, although ∼30% of all cancers harbor a Ras mutation (Prior et al., 2012), many of the same Ras mutations have also been identified in noncancerous epithelial tissue (Kumar et al.”
BackgroundAntić, Ž., Yu, J., van Reijmersdal, S. V., van Dijk, A. H. A., Dekker, L., Segerink, W. H., Sonneveld, E., Fiocco, M. F., Pieters, R., Hoogerbrugge, P. M., et al. (2020) · Haematologica · doi:10.3324/haematol.2020.259226 · Cited by 22
“Studies in other cancers have demonstrated that the prevalence of different RAS pathway mutations varies depending on the type of cancer and tissue of origin, with KRAS mutations G12D, G12V, G13D and G12C being among the most common ones.(39,40) Comparison of oncogenic capacities of different RAS hotspots has also bee…”
BackgroundHao, Q., Long, Y., Yang, Y., Deng, Y., Ding, Z., Yang, L., Shu, Y., & Xu, H. (2024) · Vaccines · doi:10.3390/vaccines12070717 · Cited by 22
“These mutations are essential for tumor survival and exhibit constitutive activation throughout the progression of the disease [146,147].”
BackgroundAlexander, P., Chan, A. H., Rabara, D., Swain, M., Larsen, E. K., Dyba, M. D., Chertov, O., Ashraf, M., Champagne, A., Lin, K. Y., et al. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110331 · Cited by 24
“Oncogenic mutations that disrupt GAP-mediated GTP hydrolysis, such as G12C, G12D, G12V, G13D, Q61H, and Q61R, are identi fi ed with varying frequencies in RAS-driven tumors (9, 11).”
Insights into cancer severity from biomolecular interaction mechanisms
Raimondi, F., Singh, G., Betts, M. J., Apic, G., Vukotic, R., Andreoné, P., Stein, L. D., & Russell, R. B. (2016) · Scientific Reports · doi:10.1038/srep34490 · Cited by 18
Morita, M., Murase, T., Okumura, Y., Ueda, K., Sakamoto, Y., Masaki, A., Kawakita, D., Tada, Y., Nibu, K., Shibuya, Y., et al. (2020) · Histopathology · doi:10.1111/his.14100 · Cited by 21
Functional diversity in the RAS subfamily of small GTPases
Astrain, G. B., Nikolova, M., & Smith, M. J. (2022) · Biochemical Society Transactions · doi:10.1042/bst20211166 · Cited by 21
Sakamoto, K., Lin, B., Nunomura, K., Izawa, T., & Nakagawa, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-12401-3 · Cited by 22
Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition
Huynh, M. V., Parsonage, D., Forshaw, T. E., Chirasani, V. R., Hobbs, G. A., Wu, H., Lee, J., Furdui, C. M., Poole, L. B., & Campbell, S. L. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102186 · Cited by 21
“Interestingly, this modification is structurally very similar to aspartic acid, a prevalent oncogenic mutant (KRAS) in human tumors (1, 22).”
BackgroundKozlova, M. I., Shalaeva, D. N., Dibrova, D. V., & Mulkidjanian, A. Y. (2022) · Biomolecules · doi:10.3390/biom12101345 · Cited by 29
Non-small-cell lung cancer-associated gene mutations and inhibitors
Kumar, A., & Kumar, A. (2022) · Advances in Cancer Biology - Metastasis · doi:10.1016/j.adcanc.2022.100076 · Cited by 21
Weng, J., Trilling, C. R., Sharma, P. K., Störmer, E., Wu, J., Herberg, F. W., & Taylor, S. S. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.167999 · Cited by 23
Ferroptosis, a subtle talk between immune system and cancer cells: To be or not to be?
Zhou, Q., Tao, C., Yuan, J., Pan, F., & Wang, R. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115251 · Cited by 21
Redox state influence on human galectin-1 function
Yu, X., Scott, S. A., Pritchard, R., Houston, T. A., Ralph, S. J., & Blanchard, H. (2015) · Biochimie · doi:10.1016/j.biochi.2015.06.013 · Cited by 21
Past, Present, and Future of Targeting Ras for Cancer Therapies
Tan, Z., & Zhang, S. (2015) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557515666151001154111 · Cited by 21
Yang, S., Yu, X., Fan, Y., Shi, X., & Jin, Y. (2018) · Journal of Cancer · doi:10.7150/jca.24425 · Cited by 23
“The rate of KRAS mutations in our result was similar to those reported in Asian populations, but was lower than those reported in Caucasian populations [19, 20].”
ResultClinical update on K-Ras targeted therapy in gastrointestinal cancers
Pant, S., Hubbard, J. M., Martinelli, E., & Bekaii‐Saab, T. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.07.011 · Cited by 21
TRPML1 and RAS-driven cancers – exploring a link with great therapeutic potential
Jung, J., & Venkatachalam, K. (2019) · Channels · doi:10.1080/19336950.2019.1666457 · Cited by 21
Protein phase separation: A novel therapy for cancer?
Wang, W., Chen, Y., Xu, A., Cai, M., Cao, J., Zhu, H., Yang, B., Shao, X., Ying, M., & He, Q. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15242 · Cited by 20
Biological Hallmarks and New Therapeutic Approaches for the Treatment of PDAC
Digiacomo, G., Volta, F., Garajová, I., Balsano, R., & Cavazzoni, A. (2021) · Life · doi:10.3390/life11080843 · Cited by 21
“All the mutations found in PDAC are activating ones and block the inactivation of KRAS [10,11] maintaining KRAS in a constitutive, GTP-bound state.”
BackgroundNeurofibromin: Protein Domains and Functional Characteristics
Scheffzek, K., & Welti, S. (2012) · Springer eBooks · doi:10.1007/978-3-642-32864-0_20 · Cited by 21
“The physiological impact of Ras regulation is underscored by the notion that Ras is mutated in a large number of human malignancies and many of the respective mutants are unable to hydrolyse GTP at a rate sufficient to terminate downstream signaling and are GAP-insensitive (Trahey and McCormick 1987; Bos et al. 1987;…”
BackgroundMuthusamy, M., Ramani, P., Arumugam, P., Rudrapathy, P., Kangusamy, B., Veeraraghavan, V. P., Jayaraman, S., Kannan, B., & Pandi, A. (2025) · BMC Oral Health · doi:10.1186/s12903-024-05406-z · Cited by 26
“They are GTPases that act as molecular switches in regulating the molecular pathways of cell proliferation and survival [23].”
A H-REV107 Peptide Inhibits Tumor Growth and Interacts Directly with Oncogenic KRAS Mutants
Han, C. W., Jeong, M. S., Ha, S. C., & Jang, S. B. (2020) · Cancers · doi:10.3390/cancers12061412 · Cited by 20
“Some 9–30% of human tumors have RAS-activating mutations, which are common in KRAS (86%), NRAS (11%), and HRAS (3”
BackgroundDiethelm‐Varela, B. (2020) · ChemMedChem · doi:10.1002/cmdc.202000756 · Cited by 22
Oncolytic Virotherapy: The Cancer Cell Side
Ehrlich, M., & Bacharach, E. (2021) · Cancers · doi:10.3390/cancers13050939 · Cited by 23
Li, C., Zhao, N., An, L., Dai, Z., Chen, X., Yang, F., You, Q., Di, B., Hu, C., & Xu, L. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.06.013 · Cited by 20
Nandi, S., Dey, R., Dey, S., Samadder, A., & Saxena, A. K. (2021) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520621666210908101751 · Cited by 20
Xiong, Y., Zeng, J., Xia, F., Cui, Q., Deng, X., & Xu, X. (2022) · Journal of Computational Chemistry · doi:10.1002/jcc.26846 · Cited by 20
Identification of KRASG12C Mutations in Circulating Tumor DNA in Patients With Cancer
Thein, K. Z., Biter, A. B., Banks, K. C., Duda, A. W., Saam, J. R., Roszik, J., Jankú, F., Skoulidis, F., Heymach, J. V., Kopetz, S., et al. (2022) · JCO Precision Oncology · doi:10.1200/po.21.00547 · Cited by 20
“KRAS is the most frequently mutated proto-oncogene, with most (approximately 80%) KRAS mutations being point mutations at codon 12.(22,23) KRAS mutations have been historically considered to be undruggable, but the discovery by Ostrem et al(24,25) of small molecules that covalently bind the shallow pocket between swit…”
BackgroundThomas, R. P., Grant, E. K., Dickinson, E. R., Zappacosta, F., Edwards, L. J., Hann, M. M., House, D., Tomkinson, N. C. O., & Bush, J. T. (2023) · RSC Medicinal Chemistry · doi:10.1039/d2md00453d · Cited by 22
Cell-Type-Specific Intracellular Protein Delivery with Inactivated Botulinum Neurotoxin
Roh, H., Dorner, B. G., & Ting, A. Y. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c01145 · Cited by 21
Ramalingam, P. S., & Arumugam, S. (2023) · Medical Oncology · doi:10.1007/s12032-023-02160-0 · Cited by 19
“(BC), colon adenocarcinoma (COAD), and lung adenocarcinoma (LUAD) and has mutational hotspots at G12 (89%), G13 (9%), and Q61 (1%) positions [1, 10].”
BackgroundOncogenic KRAS mutation confers chemoresistance by upregulating SIRT1 in non-small cell lung cancer
Shin, D. H., Jo, J. Y., Choi, M., Kim, K., Bae, Y., & Kim, S. S. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01091-0 · Cited by 21
The greedy nature of mutant RAS: a boon for drug discovery targeting cancer metabolism?
Lv, J., Wang, J., Chang, S., Liu, M., & Pang, X. (2015) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmv102 · Cited by 22
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
“small GTPases that act as molecular switches to regulate multiple pathways involved in proliferation and cell survival (1-3).”
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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