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Clinical Acquired Resistance to KRASG12C Inhibition through a Novel KRAS Switch-II Pocket Mutation and Polyclonal Alterations Converging on RAS–MAPK Reactivation
Open accessPublished version of a preprint
Abstract
Mutant-selective KRASG12C inhibitors, such as MRTX849 (adagrasib) and AMG 510 (sotorasib), have demonstrated efficacy in KRASG12C-mutant cancers, including non–small cell lung cancer (NSCLC). However, mechanisms underlying clinical acquired resistance to KRASG12C inhibitors remain undetermined. To begin to define the mechanistic spectrum of acquired resistance, we describe a patient with KRASG12C NSCLC who developed polyclonal acquired resistance to MRTX849 with the emergence of 10 heterogeneous resistance alterations in serial cell-free DNA spanning four genes (KRAS, NRAS, BRAF, MAP2K1), all of which converge to reactivate RAS–MAPK signaling. Notably, a novel KRASY96D mutation affecting the switch-II pocket, to which MRTX849 and other inactive-state inhibitors bind, was identified that interferes with key protein–drug interactions and confers resistance to these inhibitors in engineered and patient-derived KRASG12C cancer models. Interestingly, a novel, functionally distinct tricomplex KRASG12C active-state inhibitor RM-018 retained the ability to bind and inhibit KRASG12C/Y96D and could overcome resistance. Significance: In one of the first reports of clinical acquired resistance to KRASG12C inhibitors, our data suggest polyclonal RAS–MAPK reactivation as a central resistance mechanism. We also identify a novel KRAS switch-II pocket mutation that impairs binding and drives resistance to inactive-state inhibitors but is surmountable by a functionally distinct KRASG12C inhibitor. See related commentary by Pinnelli and Trusolino, p. 1874. This article is highlighted in the In This Issue feature, p. 1861
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In the citing paper
“Acquired mutations of NRAS, BRAF, RTK, and MYC were also found in patients treated with sotorasib or adagrasib monotherapy [49, 51, 53, 54].”
From Differential Response and Resistance to KRAS-Targeted Therapy (2025) · cites this paper as [54]
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
“acquired second-site Y96D mutations in KRASG12C confer clinical resistance to adagrasib by altering the switch 2 pocket such that the inhibitor can no longer bind69.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [69]
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
“Point mutations in the KRAS gene included G12D/F/R/V/W, which prevent covalent interactions with mutant cysteine, as well as V8L, G13D, V14I, Q61H, H95D/Q/R, Y96C, and Y96D [62,97,102,103].”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [103]
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
“Multiple mechanisms of acquired resistance have been identified, which largely converge on re-activation of the RAS pathway or alternatively activate parallel signaling pathways such as the PI3K/mTOR pathway10–14.”
From Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer (2024) · cites this paper as [13]
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
“We and others have recently described mechanisms of acquired resistance in patients with lung and colorectal cancer (CRC) treated with KRASG12C inhibitors, including mutations in KRAS or other RTK–RAS–MAPK pathway effectors, adaptive signaling alterations, and histologic transformation to drug-resistant cell states (14, 18–24).”
From Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer (2024) · cites this paper as [20]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Vertical reactivation of the RAS pathway elements has been observed in most samples collected from patients who developed resistance to KRASG12C inhibitors.4,8,20,21”
From Therapeutic targeting of syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers (2025) · cites this paper as [20]
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
“Genetic alterations, especially secondary RAS mutations, have been identified as one of the most common mechanisms of acquired resistance to KRAS inhibitors in patients [49, 51–55].”
From Differential Response and Resistance to KRAS-Targeted Therapy (2025) · cites this paper as [54]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In recent work, a case was described of an acquired Y96D switch II pocket mutation identified at a low variant allele frequency in ctDNA at the time of acquired resistance to adagrasib.23”
From Acquired Resistance to KRAS G12C Inhibition in Cancer (2021) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“It binds cyclophilin A, and this binary complex can associate with the active state of KRAS G12C and form a covalent bond.”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [113]
The cited source says what the claim attributes to it.
In the citing paper
“Many of the novel mutations were observed at low subclonal frequencies, contributing to tumor heterogeneity [97,103].”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [103]
The cited source says what the claim attributes to it.
In the citing paper
“While previous studies have characterized acquired resistance to KRASG12C inhibition and identified causal mutations and non-genetic mechanisms including RTK activation and epithelial-to-mesenchymal transition11–14,35, the mechanisms underlying differential sensitivity to KRASG12C inhibition are less well understood.”
From Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer (2024) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“The genetic alterations identified in these studies are highly heterogeneous and may mediate therapeutic resistance via diverse mechanisms, such as changing inhibitor binding affinity, reactivating KRAS activity, and bypassing KRAS-mediated signaling [54, 56].”
From Differential Response and Resistance to KRAS-Targeted Therapy (2025) · cites this paper as [54]
The cited source says what the claim attributes to it.
In the citing paper
“Prior studies indicated that tumors with acquired resistance to KRASG12C agents can have multiple resistance mechanisms, including alterations within the RAS/MAPK pathway and bypass activating alterations”
From Bcl-xL Is a Key Mediator of Apoptosis Following KRASG12C Inhibition in KRASG12C -mutant Colorectal Cancer (2023) · cites this paper as [29]
In the citing paper
“RM-018 (13), developed by Revolution Medicines, covalently binds to the activated state of KRASG12C mutants, forms a ternary complex with cyclophilin A and KRASG12C, thereby inhibiting their activity.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [81]
In the citing paper
“Meanwhile, RM-018 retained the ability to bind and inhibit KRASG12C/Y96D, thus overcoming drug resistance.81”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [81]
In the citing paper
“Adagrasib is a selective and irreversible oral small-molecule inhibitor of the mutant KRAS G12C protein18 and was recently approved by the FDA for treatment of NSCLC who have received at least 1 prior systemic therapy19.”
From Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non–Small Cell Lung Cancer Patients (2023) · cites this paper as [18]
In the citing paper
“Nonetheless, there remains an ongoing need for improved clinical outcomes (21), especially since emerging data indicate multiple mechanisms of acquired resistance in patients treated with sotorasib or adagrasib (22–24), many of which involve RAS pathway reactivation.”
In the citing paper
“For example, RM-018 is a covalent KRASG12C inhibitor, but through its interaction with cyclophilin A, targets KRASG12C in the GTP-bound state; hence, RM-018 is a KRASG12C-on inhibitor69.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [69]
In the citing paper
“Pan-KRAS drugs would have advantages versus mutant-selective KRAS drugs in heterogeneous cancers driven by multiple KRAS alterations at baseline or upon development of acquired resistance due to secondary KRAS on-target alterations when compared to mutant-selective inhibitors (Fig. 3), with first examples emerging in the clinic (64–66).”
From Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants (2022) · cites this paper as [65]
In the citing paper
“This has been shown preclinically with the tricomplex KRASG12C active state inhibitor RM-018 in cellular models expressing a KRASG12C Y96D double mutant variant (65).”
From Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants (2022) · cites this paper as [65]
In the citing paper
“Preclinical and clinical data suggest that resistance to KRAS p.G12C inhibition is dependent on receptor tyrosine kinase activity, especially epidermal growth factor receptor (EGFR)-signalling.29 31 32”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [32]
In the citing paper
“correlative studies conducted in other KRASG12C-mutant tumor types treated with these inhibitors have demonstrated the emergence of pleiotropic resistance through both cell autonomous and non-cell autonomous mechanisms76–78.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [77]
In the citing paper
“Thereby, KRAS (Y96D) conferred resistance to KRAS (G12C) inhibitors in patient-derived KRAS (G12C) xenografts [96].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [96]
In the citing paper
“RM-018, a neoteric KRAS (G12C) active state inhibitor, retains the ability to inhibit KRAS (G12C/Y96D) and may address the problem of drug resistance [96].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [96]
In the citing paper
“Recently, a novel KRAS (Y96D) mutation was found, which affects the switch-II pocket and reduces the H-bonding between the Y96 residue of KRAS and MRTX849.”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [96]
In the citing paper
“Interestingly, KRAS Y96D confers resistance to currently approved (non-gluelike) covalent KRAS G12C inhibitors, and RM-018 overcomes such KRAS G12C/Y96D -mediated resistance.”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [113]
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Citations
Cites
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
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
The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity
Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., Gaida, K., Holt, T., Knutson, C. G., Koppada, N., et al. (2019) · Nature · doi:10.1038/s41586-019-1694-1 · Cited by 2,277
AACR Project GENIE: Powering Precision Medicine through an International Consortium
The AACR Project GENIE Consortium, The AACR Project GENIE Consortium, André, F., Arnedos, M., Baras, A. S., Baselga, J., Bedard, P. L., Berger, M. F., Bierkens, M., Calvo, F., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0151 · Cited by 1,964
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
Hong, D. S., Fakih, M. G., Strickler, J. H., Desai, J., Durm, G. A., Shapiro, G. I., Falchook, G. S., Price, T. J., Sacher, A., Denlinger, C. S., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1917239 · Cited by 1,733
The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers
Sondka, Z., Bamford, S., Cole, C. G., Ward, S. A., Dunham, I., & Forbes, S. A. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0060-1 · Cited by 1,597
Hallin, J., Engstrom, L. D., Hargis, L., Calinisan, A., Aranda, R., Briere, D. M., Sudhakar, N., Bowcut, V., Baer, B. R., Ballard, J. A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1167 · Cited by 1,304
Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor
Janes, M. R., Zhang, J., Li, L.-S., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Darjania, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.006 · Cited by 1,172
Self-citationAnchored multiplex PCR for targeted next-generation sequencing
Zheng, Z., Liebers, M. R., Zhelyazkova, B. H., Cao, Y., Panditi, D., Lynch, K. D., Chen, J., Robinson, H. E., Shim, H. S., Chmielecki, J., et al. (2014) · Nature Medicine · doi:10.1038/nm.3729 · Cited by 913
Discovery of a Covalent Inhibitor of KRAS G12C (AMG 510) for the Treatment of Solid Tumors
Lanman, B. A., Allen, J. R., Allen, J. G., Amegadzie, A. K., Ashton, K. S., Booker, S. K., Chen, J. J., Chen, N., Frohn, M. J., Goodman, G., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01180 · Cited by 765
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Items 401–500 of 529
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Khusnutdinov, R. (2024) · Reviews and Advances in Chemistry · doi:10.1134/s2634827624600312 · Cited by 2
Shen, S., Zhang, Q., Wang, Y., Chen, H., Gong, S., Liu, Y., Gai, C., Chen, H., Zhu, E., Yang, B. H., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci185278 · Cited by 2
Personalized therapy in metastatic colorectal cancer: biomarker-driven use of biologics
Sullo, F. G., Gallio, C., Matteucci, L., Bittoni, A., Muratore, M., Esposito, L., Ceredi, B., Gallo, G., Ulivi, P., Rapposelli, I. G., et al. (2025) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2025.2556911 · Cited by 3
Liu, S., Medina-Pérez, P., Ha-Thi, M.-C., Wieland, A., Stecklum, M., Hoffmann, J., Tchernitsa, O. I., Sers, C., & Schäfer, R. (2021) · Advances in Biological Regulation · doi:10.1016/j.jbior.2021.100841 · Cited by 2
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Colombo, M., Ndembe, G., & Broggini, M. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.05.002 · Cited by 2
Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancerPreprint
Ghazi, P. C., O’Toole, K. T., Boggaram, S. S., Scherzer, M. T., Silvis, M. R., Zhang, Y., Jagannathan‐Bogdan, M., Smith, B. D., Lozano, G., Flynn, D. L., et al. (2024) · eLife · doi:10.7554/elife.96992.2 · Cited by 1
Özakıncı, H., Desai, B., Kalos, D., Chen, D., Henry, M., Solanki, H. S., Boyle, T. A., Bittar, H. E. T., Nazario, G. S., Haura, E. B., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.17.628751 · Cited by 2
Orthogonal resistance mechanisms of classical- and induced-proximity inhibitorsPreprint
Merz, M. L., Kailass, K., Pergu, R., Tran, K., Gupta, K., Severance, Z. C., Singh, S., Sreekanth, V., Law, B. K., Rosenblatt, G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.10.652755 · Cited by 2
Peng, S., Zhang, Y., Lin, X., Si, C., Van Horn, R. D., Dempsey, J. A., Goetz, E., Evans, R. J., Farber, A., Vandekopple, M. J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-72650-y · Cited by 1
Lung Cancer and KRAS -Its Molecular Biology/Genetics and Therapeutic Strategy-
Koga, T., & Mitsudomi, T. (2022) · Haigan · doi:10.2482/haigan.62.188 · Cited by 1
Targeting KRAS mutation in gastrointestinal cancers
Bicer, F., Akce, M., Piazza, G. A., Foote, J. B., & El‐Rayes, B. F. (2023) · F1000Research · doi:10.12688/f1000research.131688.1 · Cited by 1
Addicted to proteostasis: How KRAS-driven cancers acquire resistance to clinical KRAS inhibitors
Klein, A. T., & Mendillo, M. L. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2023.10.007 · Cited by 1
Pagba, C. V., Gupta, A. K., Dilsha, K. M., Sadrpour, P., Jakubec, J. L., Prakash, P., van der Hoeven, D., Cho, K., Gilbertson, S. R., & Gorfe, A. A. (2024) · ChemBioChem · doi:10.1002/cbic.202300827 · Cited by 1
Jean-Francois, F. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21861-3.00010-3 · Cited by 1
Discovery of JDQ443 (opnurasib)
Cotesta, S., & Zécri, F. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21861-3.00015-2 · Cited by 1
KRAS G12C Inhibitors: New Drugs, A New Hope
Singhal, S., Schokrpur, S., Gandara, D. R., & Riess, J. W. (2024) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2024.09.1383 · Cited by 1
Chaperone directed heterobifunctional molecules circumvent KRASG12C inhibitor resistance
Pulido, I., Luan, Q., Pastor-Puente, S., Gunder, L. C., Wang, Y., Ying, C., Li, J., Sun, Y., Dai, Y., Ascoli, C., et al. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217691 · Cited by 1
Dual Inhibitors of KRASG12D and HSP90 Are Effective against KRASG12D Inhibitor Resistance
Pulido, I., Gunder, L. C., Ying, C., Wang, Y., Dai, Y., Yang, Z., Rahnama, A., Li, J., Sun, Y., Liu, C., et al. (2025) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-1173 · Cited by 1
Targeting RAS for Cancer Treatment: What a Long, Strange Trip It's Been
Cox, A. D., & Der, C. J. (2025) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-071024-082459 · Cited by 1
M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors
Takamori, S., Haratake, N., Bhattacharya, A., Ozawa, H., Shigeta, K., Onishi, M., Nonaka, K., Komiya, T., Komatsuda, H., Takenaka, T., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03934-2 · Cited by 1
Self-citationKRAS mutated lung adenocarcinoma responds to pan-ERBB and Aurora kinase inhibitors
Uras, I. Z., Trkulja, M. V., Salama, A. K. A. A., Horvath, J., Asnani, K., Trenk, C., Kubicek, S., Bilban, M., Moll, H. P., & Casanova, E. (2026) · npj Precision Oncology · doi:10.1038/s41698-025-01242-8 · Cited by 1
Abbinantefina, A. P., Tito, C., Masciarelli, S., Tisci, G., Ceci, P., Falvo, E., Ruta, V., Panzeri, V., Sette, C., Fazi, F., et al. (2026) · Protein Science · doi:10.1002/pro.70444 · Cited by 1
Ghosh, D., Kazi, A., Vasiyani, H. K. K., Vudatha, V., Lecomte, N., Iacobuzio–Donahue, C. A., Trevino, J., & Sebti, S. M. (2026) · European Journal of Cancer · doi:10.1016/j.ejca.2026.116255 · Cited by 1
Abbinantefina, A. P., Tito, C., Masciarelli, S., Tisci, G., Sortoluzzi, S., Ceci, P., Falvo, E., Exertier, C., Troilo, F., Petrozza, V., et al. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1725088 · Cited by 1
Ma, Y.-Y., Zhang, C., Chen, Y., Zeng, L., & Zhang, X. (2026) · Blood Science · doi:10.1097/bs9.0000000000000281 · Cited by 1
KRAS and MYC synergistic inhibition: a powerful strategy targeting KRAS-mutant cancers
Yan, M., Liu, K., Xu, J., Liu, Y., Ji, L., & Zhang, S. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02659-w · Cited by 1
Liang, S., Li, Y., Wan, K., Zhang, W., & Xiong, L. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1775677 · Cited by 1
Al-Karmalawy, A. A., Attia, M. I., Yousef, T. A., Al-Qazzan, M. B., Al-Akeedi, M., Khatib, A. O. A., & Hawas, S. S. (2026) · Archiv der Pharmazie · doi:10.1002/ardp.70261 · Cited by 1
Vitale, A., Marafioti, M., Galassi, T., Madonia, G., Moro, M., & Dubois, M. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105396 · Cited by 1
Guo, Y., Zhong, Y., Hu, P., Chen, Y., Guo, W., Chen, J., Guan, P., Zhou, Z., Zhu, F., Zeng, X., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-73805-7 · Cited by 1
RAS Inhibitors: Changing the Paradigm from the Undruggable
Campana, F., Bellis, E. D., Porcaro, F., Guida, G. D., Gravara, L. D., Servetto, A., Morgillo, F., Papaccio, F., Filippelli, A., Corte, C. M. D., et al. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18070773 · Cited by 1
Li, X., Guo, Y., & Yang, S. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108367 · Cited by 1
Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance
Mathey‐Andrews, N., Rodriguez, C. L., Shui, B., Patriotis, A. L., Rideout, W. M., Chen, V. Z., Murazzi, I., Ghazi, P., Cornwall-Brady, M. R., Liu, M., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02768-8 · Cited by 1
Imaging mass cytometry in preclinical studies of lung cancer
van Maldegem, F. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-822213-3.00004-8 · Cited by 1
van Weele, L. J., Djomehri, S. I., Cai, S., Antony, J., Sikandar, S. S., Qian, D., Ho, W. H. D., West, R. B., Scheeren, F. A., & Clarke, M. F. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13220 · Cited by 1
Hamdi, A. I. F., & Stanslas, J. (2022) · ONCOLOGIE · doi:10.32604/oncologie.2022.023629 · Cited by 1
KRAS Wild-Type Pancreatic Cancer: Decoding Genomics, Unlocking Therapeutic Potential
Kato, H., Ellis, H., & Bardeesy, N. M. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-2221 · Cited by 1
Quantifying small GTPase activation status using a novel fluorescence HPLC-based assay
Araki, M., Kasuya, Y., Yoshimoto, K., Katada, T., & Kontani, K. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.108545 · Cited by 1
Misale, S., Yaeger, R. D., Mezzadra, R., Sinopoli, J. C., Bian, Y., Marasco, M., Kaplun, E., Gao, Y., Zhao, H., Paula, A. D. C., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1236956/v1 · Cited by 1
Expanding the KRASG12C Inhibitor Class: What Do We Need Next?
Norman, A., & Adjei, A. A. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.04.010 · Cited by 1
Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancerPreprint
Ghazi, P. C., O’Toole, K. T., Boggaram, S. S., Scherzer, M. T., Silvis, M. R., Zhang, Y., Jagannathan‐Bogdan, M., Smith, B. D., Lozano, G., Flynn, D. L., et al. (2024) · eLife · doi:10.7554/elife.96992.1 · Cited by 2
Challenges and opportunities of emerging mechanisms of resistance to KRASG12C inhibitors
Cecchini, M., & LoRusso, P. M. (2025) · Annals of Oncology · doi:10.1016/j.annonc.2025.03.009 · Cited by 1
Meraz, I. M., Wu, S., Xu, Y., Gao, L., Feng, M., Ren, C., Song, R., Zhang, R., Wang, Q., Xi, Y., et al. (2025) · eLife · doi:10.7554/elife.106875 · Cited by 1
Study on Driver Genes of Non-Small Cell Lung Cancer
曹, 涤. (2021) · Hans Journal of Biomedicine · doi:10.12677/hjbm.2022.121002
Data from Genomic Landscapes and Hallmarks of Mutant RAS in Human Cancers
Scharpf, R. B., Balan, A., Ricciuti, B., Fiksel, J., Cherry, C., Wang, C., Lenoue-Newton, M. L., Rizvi, H. A., White, J. R., Baras, A. S., et al. (2023) · doi:10.1158/0008-5472.c.6514292.v1
Khan, H. Y., Nagasaka, M., Li, Y., Aboukameel, A., Uddin, M. H., Sexton, R. E., Bannoura, S. F., Mzannar, Y., Hallak, M. N. A., Kim, S. H., et al. (2023) · doi:10.1158/2767-9764.c.6550541
Coates, J. T. T., Sun, S., Leshchiner, I., Thimmiah, N., Martin, E. E., McLoughlin, D. E., Danysh, B. P., Slowik, K., Jacobs, R. A., Rhrissorrakrai, K., et al. (2023) · doi:10.1158/2159-8290.c.6549032
Self-citationTarget Hyperactive ERK Signaling for Cancer Therapy
Yap, J., & Hu, J. (2023) · Springer eBooks · doi:10.1007/978-3-030-80962-1_257-1
Keats, M. A., Han, J. J. W., Lee, Y., Lee, C.-S., & Luo, J. (2023) · doi:10.1158/0008-5472.24071339
Keats, M. A., Han, J. J. W., Lee, Y., Lee, C.-S., & Luo, J. (2023) · doi:10.1158/0008-5472.24071339.v1
miRNA Profiling of 3'UTR Variations in Sporadic Lung Carcinoma TumoursPreprint
Bağcı, Ö. (2023) · Research Square · doi:10.21203/rs.3.rs-3638249/v1
Evolution of resistance to KRAS G12C inhibitor in a non-small cell lung cancer responderPreprint
Xu, J., Wang, S., Wang, Z., Huang, J., Xie, C., Cao, Y., Chen, M., & Leung, E. L. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.18.572090
Kasack, K., Metzger, P., Koch, H., Klinger, B., Malek, A. V., Tchernitsa, O. I., Gross, A., Wruck, W., Győrffy, B., Küster, B., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.04.597297
Ghazi, P. C., O’Toole, K. T., Boggaram, S. S., Scherzer, M. T., Silvis, M. R., Zhang, Y., Jagannathan‐Bogdan, M., Smith, B. D., Lozano, G., Flynn, D. L., et al. (2024) · eLife · doi:10.7554/elife.96992.2.sa0
Ghazi, P. C., O’Toole, K. T., Boggaram, S. S., Scherzer, M. T., Silvis, M. R., Zhang, Y., Jagannathan‐Bogdan, M., Smith, B. D., Lozano, G., Flynn, D. L., et al. (2024) · eLife · doi:10.7554/elife.96992.3.sa2
Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?
Healy, F. M., Turner, A. L., Marensi, V., & MacEwan, D. J. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1441938
The emergence of pan-KRAS drugs
McConnell, D. B., & Kraut, N. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21861-3.00019-x
Development of Polymer-assisted Compaction of DNA Nanoparticles for Cancer Treatment
Shen, C. (2023) · International journal of high school research · doi:10.36838/v5i7.6
A clinician’s perspective: what tumor-organoid researchers ought to know
Lim, J. U. (2025) · Organoid · doi:10.51335/organoid.2025.5.e1
Targeting RAS and associated proteins
Müller, M. P., Goody, R. S., & Rauh, D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00008-x
Meraz, I. M., Wu, S., Xu, Y., Gao, L., Feng, M., Ren, C., Song, R., Zhang, R., Wang, Q., Xi, Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.18.643954
KRAS in Stage IV Non-Small Cell Lung Cancer
(2025) · Frontiers research topics · doi:10.3389/978-2-8325-6151-5 · Cited by 1
Mechanism of Action and Research Progress of Drugs Targeting KRAS G12-Mutant Tumors
郑, 金. (2025) · World Journal of Cancer Research · doi:10.12677/wjcr.2025.152011
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Li, F., Jiang, B., Fan, X., Jiang, Z., He, J., & Liang, W. (2025) · Visualized Cancer Medicine · doi:10.1051/vcm/2025008
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(2025) · Frontiers Media SA eBooks · doi:10.3389/978-2-8325-6297-0
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Mohammadi, M., Bhat, M. A., Li, T., Wei, N., Patil, P., Mo, C., Thielen, N., Huang, Z., Du, J., Goldstein, D. Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.13.669992
Jiao, D., Chen, Y., Liu, X., Xu, W., Tang, X., Chen, J., Yan, L., & Chen, Q. (2025) · Clinical & Translational Oncology · doi:10.1007/s12094-025-04067-w
Jazieh, K., Tsai, J., Solomon, S. R., Zhu, M., Pedersen, K. S., Fernández-Zapico, M. E., & Xie, H. (2025) · Targeted Oncology · doi:10.1007/s11523-025-01191-z
Rosell, R., Lewintre, E. J., Cao, P., Cai, X., Xing, B., Ito, M., Gomez-Vazquez, J. L., Marco-Jordán, M., Fariñas, S. C., Cardona, A. F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26027462
Target Hyperactive ERK Signaling for Cancer Therapy
Yap, J., & Hu, J. (2025) · Springer eBooks · doi:10.1007/978-3-032-00771-1_257
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Baig, M. H., Jo, Y. S., Nale, S. D., Kim, C. J., Park, J., Ha, J., Moon, B., Ryu, S., & Dong, J.-J. (2026) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2025.2609342
Pereira, R. A., Oliveira, C., Tumelero, M., Fernandes, H., & Lenz, G. (2026) · Oncology Research and Treatment · doi:10.1159/000550885
Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors
Kanemura, H., Takehara, T., Maenishi, O., Tomida, S., Iwawaki, N., Kunimasa, K., Nakayama, T., Watanabe, S., Suzuki, S., Sakai, K., et al. (2026) · Cancer Research Communications · doi:10.1158/2767-9764.crc-25-0489
Luo, G., Li, D., Peng, J., Liu, R., Meng, Y., Ward, R., Zhang, Y., Zhang, X., Cui, F., Wang, J., et al. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-02798-z
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Chuikov, S., Katkam, S. K., Wang, Z., & Keshamouni, V. G. (2026) · Molecular Oncology · doi:10.1002/1878-0261.70236
Kwok, G. W., Lo, J., & Fung, T. H. W. (2026) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.70353
Kumari, U., & Divakar, S. (2026) · Journal of Emerging Technologies and Innovative Research · doi:10.56975/jetir.v13i3.578071
Chen, Y., Zhang, C.-L., Li, Y. P., Liu, C.-F., Jiang, H.-Y., Yang, Y., Wang, H., & Pang, M. (2026) · BMC Cancer · doi:10.1186/s12885-026-15946-y
Innovative targeted therapies for mosaic RAS-related vascular malformations
Morin, G. (2024) · theses.fr (ABES) · doi:10.70675/88882e5fz1bf9z4dbezae13zba4200ee9598
The analysis of targeted therapies for colorectal cancer with KRAS G12C mutation
Yin, Y. (2024) · Theoretical and Natural Science · doi:10.54254/2753-8818/61/20241491
Wu, S., Niu, J., Chen, X., Li, J., Tang, Q., Yang, Z., & Gao, S. (2026) · Clinical and Translational Medicine · doi:10.1002/ctm2.70670
Weiss, G. J., Loftus, J. C., Mallery, D. W., & Tran, N. L. (2026) · Cancers · doi:10.3390/cancers18091367
Chitneni, E., Venugopal, A., Okorie, C. O., George, A. T., Arya, A., Arias, D., Yasin, O., de Souza, L. C. P., Afshan, R., & Dave, V. A. (2026) · Cureus · doi:10.7759/cureus.108302
Lefas, A. Y., Lote, H., & Chau, I. (2026) · Precision Oncology · doi:10.3390/precisoncol1020009
SAIMSARA (2026) · SAIMSARA Journal · doi:10.62487/saimsaradc4d1e0f
Targeting ATF3-mediated asparagine biosynthesis reverses acquired resistance to KRASG12C inhibitors
Zhu, Y., Zhang, C., Li, M., Ai, L., Xu, F., Yu, Y., Yu, S., Xu, X., Liu, Q., Zhu, M., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03838-1
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Takamori, S., Haratake, N., Nonaka, K., Moriya, M., Bhattacharya, A., Takenaka, T., Yoshizumi, T., Long, M. D., & Kufe, D. W. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.20.733526
Targeting conventionally intractable cancer-driving proteins: What has been achieved recently?
Xie, Q., Xu, W., Wang, Y., & Ma, X. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119102
Weiss, G. J., Loftus, J. C., Mallery, D. W., & Tran, N. L. (2026) · Scientific Reports · doi:10.1038/s41598-026-57463-9
Evolution of resistance to KRASG12C inhibitor in a non-small cell lung cancer responder
Xu, J., Wang, S., Wang, Z. G., Huang, J., Xie, C., Zhao, T., Niu, Y., Cao, Y., Chen, M., & Leung, E. L. (2026) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2026.07.002
Azvudine enhances durable tumor control with sotorasib in a CT26-mKRAS G12C syngeneic model
Jia, L., Qin, Z., & Li, P. (2026) · Academia oncology. · doi:10.20935/acadonco8419
Yang, X., Tao, X., Qi, W., Luo, R., Lan, T., Xie, K., Cai, Y., Gao, F., Lv, Y., Liu, C., et al. (2026) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2026.101718
Arshinnikova Anna, S., Tararina Valeria, V., Zuban Polina, A., Leshcheva Elizaveta, A., Bogdanova Irena, V., Fishchenko Ekaterina, A., Nadaraia Mariam, S., Zeynalova Sabina, I., Gorodkova Maria, E., Kamurzoev Ismail, A., et al. (2026) · International Journal of Science and Research Archive · doi:10.30574/ijsra.2026.20.1.1495
KRAS-mutated Non–Small Cell Lung Cancer
Saadany, T. E., Aeschlimann, N., & Sacher, A. (2026) · The Cancer Journal · doi:10.1097/ppo.0000000000000842
ctDNA Detection of Polyclonal KRAS Resistance in Adagrasib‐Treated NSCLC
Caumeil, M., Vendrell, J. A., Cabello‐Aguilar, S., Cavaillon, S., Thomas, Q. D., & Solassol, J. (2026) · Thoracic Cancer · doi:10.1111/1759-7714.70313
Mizgalska, K., Urbaniak, K., Imbody, D. J., Haura, E. B., Guida, W. C., Branciamore, S., & Karolak, A. M. (2026) · Frontiers in Chemical Biology · doi:10.3389/fchbi.2026.1900407 · Cited by 1
Metadata
- Authors
- Tanaka, N., Lin, J. J., Li, C., Ryan, M. B., Zhang, J., Kiedrowski, L. A., Michel, A. G., Syed, M. U., Fella, K. A., Sakhi, M., Baiev, I., Juric, D., Gainor, J. F., Klempner, S. J., Lennerz, J. K., Siravegna, G., Bar-Peled, L., Hata, A. N., Heist, R. S., & Corcoran, R. B.
- Affiliations
- Harvard University (US)
- Guardant (United States) (US)
- Massachusetts General Hospital (US)
- 1Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts.
- Corresponding author
- Hata, Aaron N.
- Heist, Rebecca S.
- Corcoran, Ryan B.
- ORCID
- Venue
- Cancer Discovery
- Published
- 2021-04-06
- Volume
- 11
- Issue
- 8
- Pages
- 1913-1922
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC8338755
- OpenAlex
- W3142010099
- Cited by
- 527
- References
- 29
- Citations by year
- 2026: 85 · 2025: 100 · 2024: 124 · 2023: 91 · 2022: 86 · 2021: 41
- FWCI
- 26.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Revolution Medicines (RM-018)
- Stand Up To Cancer—American Cancer Society Lung Cancer Dream Team Translational Research Grant (SU2C-AACR-DT17–15)
- NIH (R01-CA164273, 1F32CA250231–01)
- AACR (19–20–45-BARP)
- Damon Runyon (DRR-62–20)
- NIH NCI (R00 CA215249)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- KRAS G12C, acquired drug resistance, switch-II pocket, adagrasib, sotorasib, non-small cell lung cancer, NRAS, BRAF, MEK1, drug-protein binding
- MeSH terms
- Acetonitriles, Aged, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Neoplasm Metastasis, Piperazines, Pyridines, Pyrimidines, Proto-Oncogene Proteins p21(ras), Drug Resistance, Neoplasm
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