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RAS Proteins and Their Regulators in Human Disease
Open accessAbstract
RAS proteins are binary switches, cycling between ON and OFF states during signal transduction. These switches are normally tightly controlled, but in RAS-related diseases, such as cancer, RASopathies, and many psychiatric disorders, mutations in the RAS genes or their regulators render RAS proteins persistently active. The structural basis of the switch and many of the pathways that RAS controls are well known, but the precise mechanisms by which RAS proteins function are less clear. All RAS biology occurs in membranes: a precise understanding of RAS' interaction with membranes is essential to understand RAS action and to intervene in RAS-driven diseases.
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In the citing paper
“In particular, farnesylation at the position 185 cysteine residue results in KRAS anchoring at the plasma membrane, initiating the activation of KRAS and its downstream signaling42.”
From Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization (2025) · cites this paper as [42]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Post-translational modification of KRAS plays an important role in KRAS–MAPK pathway activation.”
From Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization (2025) · cites this paper as [42]
The cited source says what the claim attributes to it.
In the citing paper
“KRAS is one of the most frequently mutated oncogenes in cancer, yet efforts to directly target KRAS have been mostly unsuccessful because initial analyses of KRAS proteins indicated that they lack a clear pocket to which small molecules can bind with high affinity [1, 2].”
From Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor (2022) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Although KRAS mutations are often collectively classified as a single oncogenic entity, distinct KRAS alleles exhibit substantial biochemical and functional heterogeneity [1,4,12].”
From Precision Targeting of KRAS-Mutant Cancers: Beyond G12C Toward G12D and Pan-RAS Therapeutic Strategies (2026) · cites this paper as [4]
In the citing paper
“Mutational activation of KRAS promotes the initiation and progression of cancers, especially in the colorectum, pancreas, lung, and blood plasma, with varying prevalence of specific activating missense mutations.”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [1]
In the citing paper
“However, it is frequently mutated in only a handful of cancers, with the highest frequencies in colorectal adenocarcinoma (COAD), lung adenocarcinoma (LUAD), multiple myeloma (MM), and pancreatic adenocarcinoma (PAAD).”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [1]
In the citing paper
“KRAS is one of the most commonly mutated genes in cancer1,2”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [1]
In the citing paper
“When mutated at one of its four hotspot codons—12, 13, 61, or 146—activated KRAS protein hyperactivates many downstream effector pathways, such as the MAPK and PI3K-AKT signaling pathways1”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [1]
In the citing paper
“As protein tyrosine phosphorylation plays an essential role in multiple intracellular processes, SHP2 is involved in the regulation of multiple signaling pathways, including those involved in cancer cells, such as RAS-MAPK, PI3K-AKT and JAK-STAT pathways.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [261]
In the citing paper
“RAS acts as a molecular switch, transmitting signals of cell growth and differentiation by binding to GTP or GDP and switching between active and inactive states.261”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [261]
In the citing paper
“abnormalities in components of the RAS pathway, including activating RAS mutations, are common across a diverse range of malignancies”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [4]
In the citing paper
“The RAS family GTPases, KRAS, NRAS and HRAS, cycle between GTP-loaded ‘on’ and GDP-loaded ‘off’ states4,6, involving the action of RAS-guanine nucleotide exchange factors (RAS-GEFs) and RAS-GTPase-activating proteins (RAS-GAPs), respectively.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [4]
In the citing paper
“Almost all cancer-associated RAS mutations (~95%) affect codon 12, 13 or 61, and lead to a markedly increased basal RAS-GTP:RAS-GDP ratio and constitutive activation of RAS effectors4,6.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [4]
In the citing paper
“When mutated, oncogenic RAS remains preferentially in the active GTP-bound state, whereas GTP hydrolysis by its GTPase function and enzymes such as GTPase-activating proteins, is compromised1,2.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [1]
In the citing paper
“KRAS in particular, is among the most frequently mutated oncogenes in cancer and is commonly associated with therapeutic resistance and poor prognosis1,5,6.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [1]
In the citing paper
“These mutations dramatically shift the equilibrium of Ras protein to exist mostly in the GTP-bound state and effectively uncouple Ras proteins from upstream receptor inputs and drive constitutive signaling to downstream Ras effector pathways (13).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [13]
In the citing paper
“On the one hand, the affinity of KRAS and GTP is at the pM level, while the concentration of GTP in cells is up to 0.5 μM.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [18]
In the citing paper
“It is difficult to achieve effective competition like protein kinase inhibitors [18, 19].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [18]
In the citing paper
“Oncogenic KRAS can activate various downstream effector pathways, and the best characterized are phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinases (MAPK) (23–25).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [24]
In the citing paper
“we recognize that these elements have a substantial influence on KRAS dynamics [53,54] and signaling [55].”
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Citations
Cites
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557
GEFs and GAPs: Critical Elements in the Control of Small G Proteins
Bos, J. L., Rehmann, H., & Wittinghofer, A. (2007) · Cell · doi:10.1016/j.cell.2007.05.018 · Cited by 1,903
The Guanine Nucleotide-Binding Switch in Three Dimensions
Vetter, I. R., & Wittinghofer, A. (2001) · Science · doi:10.1126/science.1062023 · Cited by 1,875
All ras proteins are polyisoprenylated but only some are palmitoylated
Hancock, J. F., Magee, A. I., Childs, J. E., & Marshall, C. J. (1989) · Cell · doi:10.1016/0092-8674(89)90054-8 · Cited by 1,775
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
Regulation of Small GTPases by GEFs, GAPs, and GDIs
Cherfils, J., & Zeghouf, M. (2013) · Physiological Reviews · doi:10.1152/physrev.00003.2012 · Cited by 1,245
A Cytoplasmic Protein Stimulates Normal N- ras p21 GTPase, But Does Not Affect Oncogenic Mutants
Trahey, M., & McCormick, F. (1987) · Science · doi:10.1126/science.2821624 · Cited by 1,211
Self-citationDistinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas
Cancer Genome Atlas Research Network, Campbell, J. D., Alexandrov, A., Kim, J., Wala, J., Berger, A. H., Pedamallu, C. S., Shukla, S. A., Guo, G., Brooks, A. N., et al. (2016) · Nature Genetics · doi:10.1038/ng.3564 · Cited by 1,200
Milburn, M. V., Tong, L., deVos, A. M., Brünger, A. T., Yamaizumi, Z., Nishimura, S., & Kim, S. (1990) · Science · doi:10.1126/science.2406906 · Cited by 1,062
Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane
Leevers, S. J., Paterson, H. F., & Marshall, C. J. (1994) · Nature · doi:10.1038/369411a0 · Cited by 1,011
Flagged first, then by citations
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Items 101–200 of 1,005
Sabari, J. K., Velcheti, V., Shimizu, K., Strickland, M. R., Heist, R. S., Singh, M., Nayyar, N., Giobbie‐Hurder, A., Digumarthy, S. R., Gainor, J. F., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-0383 · Cited by 138
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
New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness
Yang, H., Liang, S.-Q., Schmid, R. A., & Peng, R.-W. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00953 · Cited by 129
KRAS G13D sensitivity to neurofibromin-mediated GTP hydrolysis
Rabara, D., Tran, T. H., Dharmaiah, S., Stephens, R. M., McCormick, F., Simanshu, D. K., & Holderfield, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908353116 · Cited by 128
Self-citationQuevedo, 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
Sun, H., Ou, B., Zhao, S., Liu, X., Song, L., Liu, X., Wang, R., & Peng, Z. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.08.061 · Cited by 130
Functional characterization of a PROTAC directed against BRAF mutant V600E
Posternak, G., Tang, X., Maisonneuve, P., Jin, T., Lavoie, H., Daou, S., Orlicky, S. M., de Rugy, T. G., Caldwell, L., Chan, K., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0609-7 · Cited by 134
Kerr, D. L., Haderk, F., & Bivona, T. G. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2020.11.007 · Cited by 124
The Importance of Being PI3K in the RAS Signaling Network
Cuesta, C., Arévalo-Alameda, C., & Castellano, E. (2021) · Genes · doi:10.3390/genes12071094 · Cited by 125
Thiadiazole derivatives as anticancer agents
Szeliga, M. (2020) · Pharmacological Reports · doi:10.1007/s43440-020-00154-7 · Cited by 124
Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors
Lv, X., Lu, X., Cao, J., Luo, Q., Ding, Y., Peng, F., Pataer, A., Lu, D., Han, D., Malmberg, E., et al. (2023) · Science · doi:10.1126/science.abn4180 · Cited by 123
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
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
Mechanisms of Resistance to KRASG12C Inhibitors
Dunnett-Kane, V., Nicola, P. A., Blackhall, F. H., & Lindsay, C. R. (2021) · Cancers · doi:10.3390/cancers13010151 · Cited by 122
RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms
Yang, X., & Wu, H. K. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01631-9 · Cited by 133
König, D., Prince, S. S., & Rothschild, S. I. (2021) · Cancers · doi:10.3390/cancers13040804 · Cited by 119
Cregg, J., Edwards, A. V., Chang, S., Lee, B. J., Knox, J. E., Tomlinson, A. C. A., Marquez, A., Liu, Y., Freilich, R., Aay, N., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02314 · Cited by 128
Terrell, 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
RIT1 oncoproteins escape LZTR1-mediated proteolysis
Castel, P., Cheng, A. S., Cuevas-Navarro, A., Everman, D. B., Papageorge, A. G., Simanshu, D. K., Tankka, A. T., Galeas, J., Urisman, A., & McCormick, F. P. (2019) · Science · doi:10.1126/science.aav1444 · Cited by 114
Self-citationFerroptosis: Final destination for cancer?
Zeng, Y., Liu, W., Zhuo, Q., Hu, Q., Liu, M., Sun, Q., Zhang, Z., Fan, G., Xu, W., Ji, S., et al. (2020) · Cell Proliferation · doi:10.1111/cpr.12761 · Cited by 116
Bear, A. S., Blanchard, T., Cesare, J., Ford, M. J., Richman, L. P., Xu, C., Baroja, M. L., McCuaig, S., Costeas, C., Gabunia, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24562-2 · Cited by 113
Wong, J. C. Y., Bryant, V. L., Westover, T., Ma, J., Walsh, M., Schwartz, J. R., Alzamora, M. D. P., Mullighan, C. G., Loh, M. L., Ribeiro, R. C., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.121086 · Cited by 114
Unni, A. M., Harbourne, B., Oh, M. H., Wild, S. A., Ferrarone, J. R., Lockwood, W. W., & VARMUS, H. E. (2018) · eLife · doi:10.7554/elife.33718 · Cited by 111
Therapeutic targeting of RAS: New hope for drugging the “undruggable”
Khan, I., Rhett, J. M., & O’Bryan, J. P. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.118570 · Cited by 111
Ketcham, J. M., Haling, J. R., Khare, S., Bowcut, V., Briere, D. M., Burns, A. C., Gunn, R. J., Ivetac, A., Kuehler, J. E., Kulyk, S., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00741 · Cited by 109
Lorthiois, E., Gerspacher, M., Beyer, K. S., Vaupel, A., Leblanc, C., Stringer, R., Weiss, A., Wilcken, R., Guthy, D. A., Lingel, A., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01438 · Cited by 110
Hu, H., Cheng, R., Wang, Y., Wang, X., Wu, J., Kong, Y., Zhan, S., Zhou, Z., Zhu, H., Yu, R., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci153470 · Cited by 111
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
Cancer diagnostics based on plasma protein biomarkers: hard times but great expectations
Landegren, U. D., & Hammond, M. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12809 · Cited by 111
Li, Y., He, Y., Peng, J., Su, Z., Li, Z., Zhang, B., Ma, J., Zhuo, M., Zou, D., Liu, X., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-00134-z · Cited by 108
Suzuki, S., Yonesaka, K., Teramura, T., Takehara, T., Kato, R., Sakai, H., Haratani, K., Tanizaki, J., Kawakami, H., Hayashi, H., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0856 · Cited by 105
Arrazola Sastre, A., Luque Montoro, M., Gálvez-Martín, P., Lacerda, H. M., Lucia, A., Llavero, F., & Zugaza, J. L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176312 · Cited by 103
Longevity: Lesson from Model Organisms
Taormina, G., Ferrante, F., Vieni, S., Grassi, N., Russo, A. G., & Mirisola, M. G. (2019) · Genes · doi:10.3390/genes10070518 · Cited by 112
The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS
Li, C., Vides, A., Kim, D., Xue, J. Y., Zhao, Y., & Lito, P. (2021) · Science · doi:10.1126/science.abf1730 · Cited by 103
Young, L. C., Hartig, N., Boned del Río, I., Sari, S., Ringham-Terry, B., Wainwright, J. R., Jones, G. G., McCormick, F., & Rodriguez-Viciana, P. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720352115 · Cited by 98
Self-citationEmerging evidence and treatment paradigm of non-small cell lung cancer
Liu, S. M., Zheng, M.-M., Pan, Y., Liu, S. M., Li, Y., & Wu, Y.-L. L. C. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01436-2 · Cited by 112
SynGAP isoforms differentially regulate synaptic plasticity and dendritic development
Araki, Y., Hong, I., Gamache, T. R., Ju, S., Collado‐Torres, L., Shin, J. H., & Huganir, R. L. (2020) · eLife · doi:10.7554/elife.56273 · Cited by 97
Oncogenic 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
Combinatorial strategies to target RAS-driven cancers
Perurena, N., Situ, L., & Cichowski, K. M. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00679-6 · Cited by 107
KRAS G12V neoantigen specific T cell receptor for adoptive T cell therapy against tumors
Lu, D., Chen, Y., Jiang, M., Wang, J., Li, Y., Ma, K., Sun, W., Zheng, X., Qi, J., Jin, W., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42010-1 · Cited by 101
KRAS 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
Aberrant phase separation and cancer
Taniue, K., & Akimitsu, N. (2021) · FEBS Journal · doi:10.1111/febs.15765 · Cited by 101
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
Dietrich, P., Koch, A., FRITZ, V. K., Hartmann, A., Bosserhoff, A., & Hellerbrand, C. (2017) · Gut · doi:10.1136/gutjnl-2017-315402 · Cited by 99
Early onset sporadic colorectal cancer: Worrisome trends and oncogenic features
Cavestro, G. M., Mannucci, A., Zuppardo, R. A., Leo, M. D., Stoffel, E. M., & Tonon, G. (2018) · Digestive and Liver Disease · doi:10.1016/j.dld.2018.02.009 · Cited by 102
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Patel, M., Eckburg, A., Gantiwala, S., Hart, Z., Dein, J., Lam, K., & Puri, N. (2021) · Cancers · doi:10.3390/cancers13051115 · Cited by 104
Soriano, O., Pérez, M. A., Vicente‐Manzanares, M., & Castellano, E. (2021) · Genes · doi:10.3390/genes12060819 · Cited by 107
The molecular genetics of RASopathies : An update on novel disease genes and new disorders
Tartaglia, M., Aoki, Y., & Gelb, B. D. (2022) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.32012 · Cited by 103
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
Zhou, C., Li, C., Luo, L., Li, X., Jia, K., He, N., Mao, S., Wang, W., Shao, C., Liu, X., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.06.001 · Cited by 102
Issahaku, A. R., Mukelabai, N., Agoni, C., Rudrapal, M., Aldosari, S. M., Almalki, S. G., & Khan, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-22668-1 · Cited by 93
Spassov, D. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137124 · Cited by 116
Metabolic Plasticity of Tumor Cell Mitochondria
Cannino, G., Ciscato, F., Masgras, I., Sànchez‐Martìn, C., & Rasola, A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00333 · Cited by 97
Consensus, debate, and prospective on pancreatic cancer treatments
Wang, J., Yang, J., Narang, A. K., He, J., Wolfgang, C. L., Li, K., & Zheng, L. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01613-x · Cited by 104
Lu, H., Liu, C., Velazquez, R., Wang, H., Dunkl, L. M., Kazic-Legueux, M., Haberkorn, A., Billy, E., Manchado, E., Brachmann, S. M., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0852 · Cited by 90
“KRASmutations occur in about 30% of all cancers and account for approximately one million cancer-related deaths per year worldwide (1).”
BackgroundKobayashi, Y., Lim, S., & Yamaguchi, H. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.11.011 · Cited by 96
Adachi, Y., Kimura, R., Hirade, K., Yanase, S., Nishioka, Y., Kasuga, N., Yamaguchi, R., & Ebi, H. (2023) · Nature Cancer · doi:10.1038/s43018-023-00575-2 · Cited by 93
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Matthews, H. K., Ganguli, S., Plak, K., Taubenberger, A. V., Win, Z., Williamson, M., Piel, M., Guck, J. R., & Baum, B. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.01.004 · Cited by 95
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Cook, F. A., & Cook, S. J. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200485 · Cited by 90
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Brown, S. L., & Kendrick, S. L. (2021) · Pharmaceuticals · doi:10.3390/ph14020096 · Cited by 96
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Pino, G. L. G., Li, K., Park, E., Schmoker, A. M., Ha, B. H., & Eck, M. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2107207118 · Cited by 95
Berr, A. L., Wiese, K. M., dos Santos, G., Koch, C. M., Anekalla, K. R., Kidd, M. E., Davis, J. M., Cheng, Y., Hu, Y., & Ridge, K. M. (2023) · Oncogene · doi:10.1038/s41388-023-02703-9 · Cited by 101
Nangia, V., Siddiqui, F. M., Caenepeel, S., Timonina, D., Bilton, S. J., Phan, N., Gomez-Caraballo, M., Archibald, H. L., Li, C., Fraser, C., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0277 · Cited by 94
A gene set enrichment analysis for cancer hallmarks
Menyhárt, O., Kothalawala, W. J., & Győrffy, B. (2024) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2024.101065 · Cited by 92
Deactivation Pathway of Ras GTPase Underlies Conformational Substates as Targets for Drug Design
Lu, S., Ni, D., Wang, C., He, X., Lin, H., Wang, Z., & Zhang, J. (2019) · ACS Catalysis · doi:10.1021/acscatal.9b02556 · Cited by 90
Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers
Sulahian, R., Kwon, J. J., Walsh, K. H., Pailler, E., Bosse, T. L., Thaker, M., Almanza, D., Dempster, J. M., Pan, J., Piccioni, F., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.090 · Cited by 90
Orally effective FDA-approved protein kinase targeted covalent inhibitors (TCIs)
Roskoski, R. J. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105422 · Cited by 92
Broek, R. W. T., Eijkelenboom, A., van der Vleuten, C. J. M., Kamping, E. J., Kets, M., Verhoeven, B. H., Grünberg, K., Kool, L. J. S., Tops, B. B. J., Ligtenberg, M. J. L., et al. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22739 · Cited by 89
Robust and automated detection of subcellular morphological motifs in 3D microscopy images
Driscoll, M., Welf, E. S., Jamieson, A. R., Dean, K. M., Isogai, T., Fiolka, R. P., & Danuser, G. M. (2019) · Nature Methods · doi:10.1038/s41592-019-0539-z · Cited by 89
Targeting KRAS in Cancer: Promising Therapeutic Strategies
Mustachio, L. M., Chelariu-Raicu, A., Székvölgyi, L., & Roszik, J. (2021) · Cancers · doi:10.3390/cancers13061204 · Cited by 93
Dynamic regulation of RAS and RAS signaling
Kölch, W., Berta, D., & Rosta, E. (2023) · Biochemical Journal · doi:10.1042/bcj20220234 · Cited by 92
Properties of FDA-approved small molecule protein kinase inhibitors: A 2025 update
Roskoski, R. J. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107723 · Cited by 104
Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum
Motta, M., Pannone, L., Pantaleoni, F., Bocchinfuso, G., Radio, F. C., Cecchetti, S., Ciolfi, A., Rocco, M. D., Elting, M. W., Brilstra, E. H., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.06.018 · Cited by 90
Monaco, K., Delach, S. M., Yuan, J., Mishina, Y. M., Fordjour, P., Labrot, E., McKay, D., Guo, R., Higgins, S., Wang, H. Q., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2563 · Cited by 91
Selective and noncovalent targeting of RAS mutants for inhibition and degradation
Teng, K. W., Tsai, S. T., Hattori, T., Fedele, C., Koide, A., Yang, C., Hou, X., Zhang, Y., Neel, B. G., O’Bryan, J. P., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22969-5 · Cited by 89
Drugging “undruggable” genes for cancer treatment: Are we making progress?
Duffy, M. J., & Crown, J. P. (2020) · International Journal of Cancer · doi:10.1002/ijc.33197 · Cited by 86
PROTAC therapy as a new targeted therapy for lung cancer
Li, J. W., Zheng, G., Kaye, F. J., & Wu, L. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2022.11.011 · Cited by 87
Bröker, J., Waterson, A. G., Smethurst, C., Kessler, D., Böttcher, J., Mayer, M., Gmaschitz, G., Phan, J., Little, A., Abbott, J. R., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01120 · Cited by 96
Strategies to tackle RAS-mutated metastatic colorectal cancer
Patelli, G., Tosi, F., Amatu, A., Mauri, G., Curaba, A., Patanè, D. A., Pani, A., Scaglione, F., Siena, S., & Sartore-Bianchi, A. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100156 · Cited by 86
Emerging therapeutic targets for neurofibromatosis type 1
Walker, J. A., & Upadhyaya, M. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2018.1465931 · Cited by 90
HRAS‐driven cancer cells are vulnerable to TRPML1 inhibition
Jung, J., Cho, K., Naji, A. K., Clemons, K., Wong, C., Villanueva, M., Gregory, S., Karagas, N. E., Tan, L., Hong, L., et al. (2019) · EMBO Reports · doi:10.15252/embr.201846685 · Cited by 85
The Ras switch in structural and historical perspective
Gasper, R., & Wittinghofer, F. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0330 · Cited by 92
Channeling the Force: Piezo1 Mechanotransduction in Cancer Metastasis
Dombroski, J. A., Hope, J. M., Sarna, N. S., & King, M. R. (2021) · Cells · doi:10.3390/cells10112815 · Cited by 94
Pantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., & Poso, A. (2018) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1006458 · Cited by 85
Mo, S. P., Coulson, J. M., & Prior, I. A. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180173 · Cited by 85
Radio Signals from Live Cells: The Coming of Age of In-Cell Solution NMR
Luchinat, E., Cremonini, M., & Banci, L. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00790 · Cited by 86
A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers
Cheng, R., Li, F., Zhang, M., Xia, X., Wu, J., Gao, X., Zhou, H., Zhang, Z., Huang, N., Yang, X., et al. (2022) · Cell Research · doi:10.1038/s41422-022-00726-7 · Cited by 87
Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS
Yin, G., Huang, J., Petela, J., Jiang, H., Zhang, Y., Gong, S., Wu, J., Liu, B., Shi, J., & Gao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01441-4 · Cited by 98
Inhibitors of BRAF dimers using an allosteric site
Cotto-Rios, X. M., Agianian, B., Gitego, N., Zacharioudakis, E., Giricz, O., Wu, Y., Zou, Y., Verma, A. K., Poulikakos, P. I., & Gavathiotis, E. (2020) · Nature Communications · doi:10.1038/s41467-020-18123-2 · Cited by 87
Xu, W., Deng, B., Lin, P., Liu, C., Li, B., Huang, Q.-J., Zhou, H., Yang, J., & Qu, L. (2019) · Science China Life Sciences · doi:10.1007/s11427-019-9580-5 · Cited by 85
Structure–function analysis of the SHOC2–MRAS–PP1C holophosphatase complex
Kwon, J. J., Hajian, B., Bian, Y., Young, L. C., Amor, A. J., Fuller, J. R., Fraley, C. V., Sykes, A. M., So, J., Pan, J., et al. (2022) · Nature · doi:10.1038/s41586-022-04928-2 · Cited by 79
Self-citationMAPK Signaling Pathway in Oral Squamous Cell Carcinoma: Biological Function and Targeted Therapy
Cheng, Y., Chen, J., Shi, Y., Fang, X., & Tang, Z. (2022) · Cancers · doi:10.3390/cancers14194625 · Cited by 85
Kazi, A., Xiang, S., Yang, H., Chen, L., Kennedy, P., Ayaz, M., Fletcher, S., Cummings, C., Lawrence, H. R., Beato, F., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3399 · Cited by 81
SOS GEFs in health and disease
Baltanás, F. C., Zarich, N., Rojas-Cabañeros, J. M., & Santos, E. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188445 · Cited by 100
Rauen, K. A. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049344 · Cited by 84
Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and InteractionsPreprint
Scheffzek, K., & Shivalingaiah, G. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031500 · Cited by 83
Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges
Tang, D., Kroemer, G., & Kang, R. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01422-7 · Cited by 80
Lee, J. W., Zhang, Y. X., Eoh, K. J., Sharma, R., Sanmamed, M. F., Wu, J. Q., Choi, J., Park, H. S., Iwasaki, A., Kaftan, E. J., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.02.004 · Cited by 81
The Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases
Qu, L., Pan, C., He, S., Lang, B., Gao, G.-D., Wang, X., & Wang, Y. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00121 · Cited by 84
Lanfredini, S., Thapa, A., & O’Neill, E. E. (2019) · Biochemical Society Transactions · doi:10.1042/bst20170521 · Cited by 78
Metadata
- Authors
- Simanshu, D. K., Nissley, D. V., & McCormick, F.
- Affiliations
- Frederick National Laboratory for Cancer Research (US)
- University of California, San Francisco (US)
- Corresponding author
- McCormick, Frank
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 170
- Issue
- 1
- Pages
- 17-33
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5555610
- OpenAlex
- W2732767128
- Cited by
- 1,943
- References
- 162
- Citations by year
- 2026: 210 · 2025: 263 · 2024: 276 · 2023: 247 · 2022: 267 · 2021: 247 · 2020: 194 · 2019: 143 · 2018: 82 · 2017: 12
- FWCI
- 11.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute
- NIH (HHSN261200800001E)
- Outstanding Investigator Award (5R35CA197709)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Ras proteins, Ras signaling, RASopathies, cancer, mental illness, RAS mutations, signal transduction, membrane binding, Ras activation
- MeSH terms
- Congenital Abnormalities, Animals, Mental Disorders, Cell Membrane, Humans, Mutation, Neoplasms, Phylogeny, Yeasts, Signal Transduction, ras Proteins
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