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Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism
Open accessAbstract
Cancer therapy by entrapment: Mutations in the KRAS oncogene occur at high frequency in several of the most lethal human cancers, including lung and pancreatic cancer. Substantial effort has thus been directed toward developing KRAS inhibitors. KRAS encodes an enzyme that binds the nucleotide GTP and hydrolyzes it to GDP. It had been thought that oncogenic mutations disable this hydrolytic activity, locking KRAS in the GTP-bound, active state. Surprisingly, Lito et al. found that a certain KRAS mutant (G12C) retains hydrolytic activity and continues to cycle between its active and inactive states. They describe a compound that inhibits KRAS(G12C) signaling and tumor cell growth by binding to the GDPbound form of KRAS, trapping it in its inactive state. Science , this issue p. 604
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“early preclinical studies with KRASG12C inhibitors, such as ARS-1620, have suggested a potential role for adaptive feedback as a mechanism of resistance (7) (15).”
From Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition (2020) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“First, as described by Lito et al, increased RTK activity may lead to increased cycling of KRASG12C to its active GTP-bound form that hinders the binding of most KRASG12C inhibitors, which bind specifically to the inactive GDP-bound form (7).”
From Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition (2020) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“compounds have been identified that bind covalently to cysteine 12 within the switch II pocket of the GDP-bound form of the KRASG12C protein, preventing oncogenic signaling and causing potent tumor regressions in preclinical models.3-7”
From Acquired Resistance to KRAS G12C Inhibition in Cancer (2021) · cites this paper as [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, the appreciable degree of nucleotide cycling observed in KRAS G12C -mutant protein proved critical for the development of clinically active KRAS G12C -selective inhibitors which bind the GDP-bound conformation and lock KRAS in the inactive state [7-9].”
From Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor (2022) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Preclinical studies have identified EGFR as a major mediator of adaptive feedback, and concomitant blockade of EGFR has been shown to enhance the antitumor activity of KRAS G12C inhibition12,15.”
From Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial (2024) · cites this paper as [15]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“The inhibitors function by locking KRASG12C in an inactive GDP bound state, exploiting the unique property of KRASG12C to cycle between the GDP- and GTP-bound states (6,7).”
From Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition (2020) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“These resistance mutations probably increase the fraction of KRAS protein in the active GTP-bound form that does not bind to the drug.4”
From Acquired Resistance to KRAS G12C Inhibition in Cancer (2021) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Preclinical studies have identified EGFR as a major mediator of adaptive feedback, and concomitant blockade of EGFR has been shown to enhance the antitumor activity of KRAS G12C inhibition12,15.”
From Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial (2024) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Given this particular feature of the KRAS G12C mutant protein, the efficacy of these compounds can be increased by concomitant receptor tyrosine kinase (RTK) inhibition that further maintain KRAS G12C in a GDP-bound conformation, facilitating the binding of the covalent inhibitor(7-9).”
From EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer. (2020) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“It is known that RTK inhibition in NSCLC preclinical models can potentiate KRAS G12C covalent inhibitors, by slowing down exchange factors favoring a GDP-bound status of KRAS(8).”
From EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer. (2020) · cites this paper as [8]
In the citing paper
“ARS-853 was firstly selected as a potent inhibitor that suppresses K-RasG12C-dependent cell proliferation.4,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“The binding of these compounds to K-RasG12C induces structurally disordered switch I/II, which converts the GTP preference of naive K-RasG12C to GDP.”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“However, it failed to demonstrate in vivo efficacy due to undesirable pharmacokinetics.4,5,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“Consequently, a large fraction of K-RasG12C protein is trapped in the inactive GDP-bound state, which impairs its interaction with downstream effectors, such as rapidly accelerated fibrosarcoma kinase (RAF).3,4,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“For example, secondary KRAS mutations would confer intrinsic resistance to ARS-853 in KRASG12C mutant models by either potentiating nucleotide exchange (secondary mutation: Y40A, N116H, or A146V) or impairing inherent GTPase activity (secondary mutation: A59G, Q61L, or Y64A) (Figure 3D).49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“Instead, K-RasG12C inhibitors act primarily through targeting MAPK/ERK pathway for growth inhibition.4, 5, 6, 7,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“These preclinical findings strongly imply that intrinsic resistance might be accountable for the heterogeneous responses to K-RasG12C inhibition in the clinic.4, 5, 6, 7,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“In most KRASG12C mutant models, the phosphorylation status of AKT and mTORC1-effector ribosomal protein S6 is barely affected by K-RasG12C inhibition.6,7,12,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“In line with the these findings, inconsistent results were observed co-treating KRASG12C mutant cancer cells with K-RasG12C inhibitors plus either MEK or ERK inhibitors, limiting the use of these drug combinations in the clinic.6,12,49”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“Lito et al.49 reported that the effect of ARS-853 was potentiated by EGFR inhibition in H2122 and Calu-1 cells.”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [49]
In the citing paper
“improvements in drug design have culminated in the development of inhibitors that are selective for mutant KRAS in its active or inactive state.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [65]
In the citing paper
“Accordingly, inhibitors of this type are KRASG12C specific; therefore, they do not affect RAS signalling in non-malignant cells65,70–72 and, at least theoretically, have a low risk of on-target, off-tumour toxicities.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [65]
In the citing paper
“KRASG12C is not permanently GTP-bound and maintains a dependency on upstream receptor tyrosine kinase (RTK) signaling for GEF-mediated GTP reloading (9, 10).”
From Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants (2022) · cites this paper as [9]
In the citing paper
“The rationale for pursuing SHP2 and SOS1 inhibitors as pan-KRAS inhibitors is grounded in the evidence that several (K)RAS oncoproteins, including KRASG12C, still cycle between an inactive and active state and rely on upstream activation and nucleotide exchange to exhibit their full transforming potential (9–13, 33, 34).”
From Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants (2022) · cites this paper as [9]
In the citing paper
“G12C-Is bind an evanescent pocket in KRAS-GDP, positioning a reactive group to couple to the mutant cysteine.”
From SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling (2021) · cites this paper as Lito et al., 2016
In the citing paper
“follow-up studies indicated that these initial compounds showed only limited potency (39, 40).”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [39]
In the citing paper
“Binding of compound 12 to the switch II pocket impaired KRAS signalling by shifting nucleotide affinity from favouring GTP to GDP and led to the accumulation of KRAS in its inactive state91.”
From Advances in covalent drug discovery (2022) · cites this paper as [91]
In the citing paper
“Still, the mutant KRAS undergoes GDP–GTP cycling [5].”
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Citations
Cites
Cell Signaling by Receptor Tyrosine Kinases
Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
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
Niesen, F., Berglund, H., & Vedadi, M. (2007) · Nature Protocols · doi:10.1038/nprot.2007.321 · Cited by 2,420
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997
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
RAS oncogenes: weaving a tumorigenic web
Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3106 · Cited by 1,789
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
Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
Pao, W., & Chmielecki, J. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2947 · Cited by 1,083
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Suzuki, T., Kishikawa, T., Sato, T., Takeda, N., Sugiura, Y., Seimiya, T., Sekiba, K., Ohno, M., Iwata, T., Ishibashi, R., et al. (2021) · Cancer Gene Therapy · doi:10.1038/s41417-021-00326-4 · Cited by 28
Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers
Cekani, E., Epistolio, S., Dazio, G., Cefalì, M., Wannesson, L., Frattini, M., & Froesch, P. (2022) · Cancers · doi:10.3390/cancers14174103 · Cited by 27
CRISPR prime editing for unconstrained correction of oncogenic KRAS variants
Jang, G., Kweon, J., & Kim, Y. (2023) · Communications Biology · doi:10.1038/s42003-023-05052-1 · Cited by 30
Yang, L., Li, Z., Binzel, D. W., Guo, P., & Williams, T. M. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.07.027 · Cited by 29
Li, Z., Shao, C., Liu, X., Lu, X., Jia, X., Zheng, X., Wang, S., Zhu, L., Li, K., Pang, Y., et al. (2019) · Carcinogenesis · doi:10.1093/carcin/bgz086 · Cited by 26
Lokhandwala, J., Smalley, T. B., & Tran, T. H. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1394702 · Cited by 28
Plangger, A., Rath, B., Hochmair, M. J., Funovics, M. A., & Hamilton, G. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101230 · Cited by 24
Li, H., Qi, W.-L., Wang, Y., & Meng, L. (2021) · Genes & Diseases · doi:10.1016/j.gendis.2021.08.011 · Cited by 28
Hu, Z., & Martí, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213865 · Cited by 25
RAS‐targeted cancer therapy: Advances in drugging specific mutations
Liu, C., Ye, D., Yang, H., Chen, X., Su, Z., Li, X., Ding, M., & Liu, Y. (2023) · MedComm · doi:10.1002/mco2.285 · Cited by 25
Molecular subtype specific efficacy of MEK inhibitors in pancreatic cancers
Brauswetter, D., Gurbi, B., Varga, A., Várkondi, E., Schwab, R. B., Bánhegyi, G., Fábián, O., Kéri, G., Valyi-Nagy, I. T., & Peták, I. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185687 · Cited by 26
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
SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition
Song, X., Zhou, Z., Elmezayen, A., Wu, R., Yu, C., Gao, B., Minna, J. D., Westover, K. D., Zeh, H. J., Kroemer, G., et al. (2024) · Science Advances · doi:10.1126/sciadv.adq4274 · Cited by 26
A treatment strategy for KRAS-driven tumors
Mai, T. T., & Lito, P. (2018) · Nature Medicine · doi:10.1038/s41591-018-0111-x · Cited by 24
Self-citationWang, X. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c00844 · Cited by 23
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Kilowski, K. A., Dietrich, M. F., Xiu, J., Baca, Y., Hinton, A. C., Ahmad, S., Herzog, T. J., Thaker, P. H., & Holloway, R. W. (2024) · Gynecologic Oncology · doi:10.1016/j.ygyno.2024.10.026 · Cited by 23
Liu, K., Guo, J., Liu, K., Fan, P., Zeng, Y., Xu, C., Zhong, J., Li, Q., & Zhou, Y. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.034 · Cited by 23
Khan, I., Koide, A., Zuberi, M., Ketavarapu, G., Denbaum, E., Teng, K. W., Rhett, J. M., Spencer-Smith, R., Hobbs, G. A., Camp, E. R., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110322 · Cited by 24
Advances in Immunosuppressive Agents Based on Signal Pathway
Xu, Z., & Chu, M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.917162 · Cited by 24
Co-targeting KRAS G12C and EGFR reduces both mutant and wild-type RAS-GTP
McFall, T. B., Trogdon, M., Guizar, A. C., Langenheim, J. F., Sisk-Hackworth, L., & Stites, E. C. (2022) · npj Precision Oncology · doi:10.1038/s41698-022-00329-w · Cited by 25
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Yang, S., Xia, J., Yang, Z., Xu, M., & Li, S. (2021) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2021.100311 · Cited by 23
Evolution of direct RAS inhibitors: from undruggable target to clinical breakthroughs
Wang, X., Wu, J., Xiao, A., Wang, J., & Tian, J. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02364-0 · Cited by 25
Disrupted molecular glue complex drives RAS inhibitor resistance
Sang, B., Ye, L. F., Fu, Z., Pourfarjam, Y., Cuevas-Navarro, A., Fan, S., Hu, F., Washington, A., Rodriguez, D. J., Vides, A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.031 · Cited by 43
Self-citationYang, X., Chen, Y., Zhou, Y., Wu, C., Li, Q., Wu, J., Hu, W., Zhao, W., Wei, W., Wu, C. P., et al. (2021) · Oncogene · doi:10.1038/s41388-021-01837-y · Cited by 22
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
Fluorescent Biosensor for Measuring Ras Activity in Living Cells
Weeks, R., Zhou, X., Yuan, T. L., & Zhang, J. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c05203 · Cited by 24
Direct 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
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Mons, E., Kim, R. Q., & Mulder, M. P. C. (2023) · Pharmaceuticals · doi:10.3390/ph16040547 · Cited by 23
Sharma, A. K., Pei, J., Yang, Y., Dyba, M. D., Smith, B. D., Rabara, D., Larsen, E. K., Lightstone, F. C., Esposito, D., Stephen, A. G., et al. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.105650 · Cited by 25
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Zhao, Y., Xue, J. Y., & Lito, P. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1331 · Cited by 21
Self-citationSaturno, G., Lopes, F., Niculescu-Duvaz, I., Niculescu-Duvaz, D., Zambon, A., Davies, L., Johnson, L., Preece, N., Lee, R., Viros, A., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2020.10.483 · Cited by 21
Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds?
Tao, H., Yang, B., Farhangian, A., Xu, K., Li, T., Zhang, Z., & Li, J. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02760 · Cited by 21
Sciver, R. E. V., Lee, M., Lee, C. G. L., Lafever, A., Svyatova, E. A., Kanda, K., Collier, A. L., van Reesema, L. L. S., Tang-Tan, A. M., Zheleva, V. P., et al. (2018) · Cancers · doi:10.3390/cancers10050142 · Cited by 21
Recent advances in the biology and therapy of medullary thyroid carcinoma
Nelkin, B. D. (2017) · F1000Research · doi:10.12688/f1000research.12645.1 · Cited by 21
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Ricciardiello, F., Bergamaschi, L., Vitto, H. D., Yang, G., Zhang, T., Palorini, R., & Chiaradonna, F. (2021) · Cells · doi:10.3390/cells10020431 · Cited by 21
Chen, X., Zou, F., Hu, Z., Du, G., Yu, P., Wang, W., Wang, H., Ye, L., & Tian, J. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115019 · Cited by 20
KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients
Garzón, M., Villatoro, S., Teixidó, C., Mayo, C., Martínez, A., Gil, M. D. L. L., Viteri, S., Morales-Espinosa, D., & Rosell, R. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.10.14 · Cited by 19
Sacco, A., Federico, C., Todoerti, K., Ziccheddu, B., Palermo, V., Giacomini, A., Ravelli, C., Maccarinelli, F., Bianchi, G., Belotti, A., et al. (2021) · Blood · doi:10.1182/blood.2020010572 · Cited by 20
Global profiling of AMG510 modified proteins identified tumor suppressor KEAP1 as an off-target
Wang, Y., Zhong, B., Xu, C., Zhan, D., Zhao, S., Wu, H., Liu, M., Lan, X., Cai, D., Ding, Q., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106080 · Cited by 19
Inhibition of RAS: proven and potential vulnerabilities
Zuberi, M., Khan, I., & O’Bryan, J. P. (2020) · Biochemical Society Transactions · doi:10.1042/bst20190023 · Cited by 20
Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer
Lee, J. J., Jain, V., & Amaravadi, R. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212402 · Cited by 20
Quantitative Systems Pharmacology Analysis of KRAS G12C Covalent Inhibitors
Stites, E. C., & Shaw, A. S. (2018) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12291 · Cited by 20
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Than, M. T., O’Hara, M. H., Stanger, B. Z., & Reiss, K. A. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-23-0519 · Cited by 22
Karaboga, H., Huang, W., Srivastava, S., Widmann, S., Addanki, S., Gamage, K. T., Mazhar, Z., Ebalunode, J. O., Briggs, J. M., Gustafsson, J.-Α., et al. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.0c00546 · Cited by 19
Vaclová, T., Chakraborty, A., Sherwood, J. L., Ross, S. J., Carroll, D. K., Barrett, J. C., Downward, J., & de Bruin, E. C. (2022) · Scientific Reports · doi:10.1038/s41598-022-06369-3 · Cited by 20
Mahran, R., Kapp, J. N., Valtonen, S., Champagne, A., Ning, J., Gillette, W., Stephen, A. G., Hao, F., Plückthun, A., Härmä, H., et al. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00315 · Cited by 20
The extended spectrum of RAS‐MAPK pathway mutations in colorectal cancer
Costigan, D. C., & Dong, F. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22813 · Cited by 21
Emaus, M. N., Zhu, C., & Anderson, J. L. (2019) · Analytica Chimica Acta · doi:10.1016/j.aca.2019.10.057 · Cited by 19
Li, Z., & Buck, M. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.9b00690 · Cited by 19
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Marín‐Ramos, N. I., Piñar, C., Vázquez‐Villa, H., Martín‐Fontecha, M., González, Á., Canales, Á., Algar, S., Mayo, P. P., Jiménez‐Barbero, J., Gajate, C., et al. (2016) · Chemistry - A European Journal · doi:10.1002/chem.201604905 · Cited by 19
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Akhave, N. S., Biter, A. B., & Hong, D. S. (2022) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-22-0356 · Cited by 17
Qi, W.-L., Li, H.-Y., Wang, Y., Xu, L., Deng, J.-T., Zhang, X., Wang, Y.-X., & Meng, L.-H. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-01015-0 · Cited by 19
Chowdhury, S., Xiu, J., Ribeiro, J. R., Nicolaides, T. P., Zhang, J., Korn, W. M., Poorman, K. A., Lenz, H., Marshall, J. L., Oberley, M. J., et al. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02826-0 · Cited by 20
NF1 loss of function as an alternative initiating event in pancreatic ductal adenocarcinoma
Ramakrishnan, G., Parajuli, P., Singh, P., Friend, C., Hurwitz, E. G., Prunier, C., Razzaque, M. S., Xu, K., & Atfi, A. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111623 · Cited by 19
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Liu, J., Mroczek, M., Mach, A., Stępień, M., Aplas, A., Pronobis‐Szczylik, B., Bukowski, S., Mielczarek, M., Gajewska, E., Topolski, P., et al. (2023) · Cancers · doi:10.3390/cancers15030779 · Cited by 18
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Khan, S. U., Budamagunta, V., & Zhou, D. (2023) · Advances in cancer research · doi:10.1016/bs.acr.2023.02.004 · Cited by 21
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Giopanou, I., & Pintzas, A. (2020) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.102859 · Cited by 17
Attili, I., Corvaja, C., Aliaga, P. T., Signore, E. D., Spitaleri, G., Passaro, A., & de Marinis, F. (2025) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2025.102957 · Cited by 19
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Wang, Q., Xu, C., Cai, R., An, W., Yuan, H., & Xu, M. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13290 · Cited by 19
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Manabe, T., & Bivona, T. G. (2022) · Journal of Clinical Investigation · doi:10.1172/jci156891 · Cited by 17
Yang, W., Meng, L., Chen, K., Tian, C., Peng, B., Zhong, L., Zhang, C., Yang, X., Zou, J., Yang, S., et al. (2019) · Cancer Science · doi:10.1111/cas.13929 · Cited by 17
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Metadata
- Authors
- Lito, P., Solomon, M., Li, L.-S., Hansen, R., & Rosen, N.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Wellspring Biosciences (United States) (US)
- Corresponding author
- Lito, Piro
- Rosen, Neal
- Venue
- Science
- Published
- 2016-02-05
- Volume
- 351
- Issue
- 6273
- Pages
- 604-608
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4955282
- OpenAlex
- W2233032895
- Semantic Scholar
- e165d3c03cf60d1cdc247a235e53363d62727803
- Cited by
- 691
- References
- 38
- Citations by year
- 2026: 53 · 2025: 62 · 2024: 69 · 2023: 75 · 2022: 86 · 2021: 92 · 2020: 71 · 2019: 58 · 2018: 47 · 2017: 49 · 2016: 29
- FWCI
- 31.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P01CA129243-06, K08CA191082-01A1)
- Memorial Sloan Kettering Cancer Center Experimental Therapeutics (SKI12103)
- LUNGevity Foundation Career Development Award
- V Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- KRAS G12C, GTPase activity, nucleotide exchange, KRAS-driven cancers, tyrosine kinase signaling, tumor cell growth inhibition
- MeSH terms
- Adenocarcinoma of Lung, Adenocarcinoma, Alleles, Antineoplastic Agents, Azetidines, Cysteine, Cytidine Diphosphate, Enzyme Inhibitors, Glycine, Guanosine Triphosphate, Humans, Lung Neoplasms, Mutation, Piperazines, Protein Conformation, Time Factors, Proto-Oncogene Proteins p21(ras), Cell Line, Tumor, HEK293 Cells, Molecular Targeted Therapy
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