CRISPR Screening Identifies Mechanisms of Resistance to KRASG12C and SHP2 Inhibitor Combinations in Non-Small Cell Lung Cancer
Open accessPublished version of a preprint
Abstract
Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated non–small cell lung cancer (NSCLC) and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 ± TNO155, alone or combined with the PI3Kα inhibitor alpelisib and/or the cyclin-dependent kinase 4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition. Tumor regression by single-agent JDQ443 at clinically relevant doses lasted on average 2 weeks and was increasingly extended by the double, triple, or quadruple combinations. Growth resumption was accompanied by progressively increased KRAS G12C amplification. Functional genome-wide CRISPR screening in KRASG12C-dependent NSCLC lines with distinct mutational profiles to identify adaptive mechanisms of resistance revealed sensitizing and rescuing genetic interactions with KRASG12C/SHP2 coinhibition; FGFR1 loss was the strongest sensitizer, and PTEN loss the strongest rescuer. Consistently, the antiproliferative activity of KRASG12C/SHP2 inhibition was strongly enhanced by PI3K inhibitors. Overall, KRAS G12C amplification and alterations of the MAPK/PI3K pathway were predominant mechanisms of resistance to combined KRASG12C/SHP2 inhibitors in preclinical settings. The biological nodes identified by CRISPR screening might provide additional starting points for effective combination treatments. Significance: Identification of resistance mechanisms to KRASG12C/SHP2 coinhibition highlights the need for additional combination therapies for lung cancer beyond on-pathway combinations and offers the basis for development of more effective combination approaches. See related commentary by Johnson and Haigis, p. 4005
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
KRAS G12C inhibitors activate RHOA signaling, which drives YAP nuclear localization and enhances tumor survival via YAP/TEAD activity.
“KRAS G12C inhibitors activate RHOA signaling, which drives YAP nuclear localization and enhances tumor survival via YAP/TEAD activity.”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [73]
Inhibiting TEAD synergistically enhances the efficacy of KRAS G12C inhibitors.
“inhibiting TEAD has been shown to synergistically enhance the efficacy of KRAS G12C inhibitors [73]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [73]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
The cancer genome atlas pan-cancer analysis project
The Cancer Genome Atlas Research Network, Weinstein, J. N., Collisson, E. A., Mills, G. B., Shaw, K. R. M., Ozenberger, B. A., Ellrott, K., Shmulevich, I., Sander, C., & Stuart, J. M. (2013) · Nature Genetics · doi:10.1038/ng.2764 · Cited by 9,092 · see citing works
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950 · see citing works
Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship
Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008) · Mayo Clinic Proceedings · doi:10.4065/83.5.584 · Cited by 3,927 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278 · see citing works
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 · see citing works
The Fibroblast Growth Factor signaling pathway
Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050 · cited 2× · see citing works
“…CRISPR data show FGF activity to be implicated in attenuating KRAS G12C i þ SHP2i response, both directly via the sensitizing effect of FGFR1 knockout and indirectly through the bio-synthesis of heparan sulfate proteoglycans, which act as coreceptors for FGFR1 and other signaling receptors (42).”
BackgroundGEFs 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 · see citing works
RAS oncogenes: the first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902 · see citing works
Sotorasib for Lung Cancers with <i>KRAS</i> p.G12C Mutation
Skoulidis, F., Li, B. T., Dy, G. K., Price, T. J., Falchook, G. S., Wolf, J., Italiano, A., Schuler, M., Borghaei, H., Barlesi, F., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103695 · Cited by 1,849 · see citing works
KRAS <sup>G12C</sup> 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 · see citing works
Hyperactive Ras in developmental disorders and cancer
Schubbert, S., Shannon, K., & Bollag, G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2109 · Cited by 1,583 · see citing works
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 · see citing works
Acquired Resistance to KRAS <sup>G12C</sup> Inhibition in Cancer
Awad, M. M., Liu, S., Rybkin, I. I., Arbour, K. C., Dilly, J., Zhu, V. W., Johnson, M. L., Heist, R. S., Patil, T., Riely, G. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105281 · Cited by 1,247 · see citing works
Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth
Zanconato, F., Forcato, M., Battilana, G., Azzolin, L., Quaranta, E., Bodega, B., Rosato, A., Bicciato, S., Cordenonsi, M., & Piccolo, S. (2015) · Nature Cell Biology · doi:10.1038/ncb3216 · Cited by 1,219 · see citing works
Adagrasib in Non–Small-Cell Lung Cancer Harboring a <i> KRAS <sup>G12C</sup> </i> Mutation
Jänne, P. A., Riely, G. J., Gadgeel, S. M., Heist, R. S., Ou, S.-H. I., Pacheco, J. M., Johnson, M. L., Sabari, J. K., Leventakos, K., Yau, E., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2204619 · Cited by 1,061 · see citing works
Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases
Chen, Y.-N. P., LaMarche, M. J., Chan, H. M., Fekkes, P., Garcia-Fortanet, J., Acker, M. G., Antonakos, B., Chen, C. H.-T., Chen, Z., Cooke, V. G., et al. (2016) · Nature · doi:10.1038/nature18621 · Cited by 925 · see citing works
Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations
Hunter, J. C., Manandhar, A., Carrasco, M. A., Gurbani, D., Gondi, S., & Westover, K. D. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0203 · Cited by 786 · see citing works
Folkes, A. J., Ahmadi, K., ALDERTON, W. K., Alix, S., Baker, S. J., Box, G., Chuckowree, I., Clarke, P. A., Depledge, P., Eccles, S. A., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm800295d · Cited by 756 · see citing works
ColonyArea: An ImageJ Plugin to Automatically Quantify Colony Formation in Clonogenic Assays
Guzmán, C., Bagga, M., Kaur, A., Westermarck, J. K., & Abankwa, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092444 · Cited by 720 · see citing works
Yap1 Activation Enables Bypass of Oncogenic Kras Addiction in Pancreatic Cancer
Kapoor, A., Yao, W., Ying, H., Hua, S., Liewen, A., Wang, Q., Zhong, Y., Wu, C.-J., Sadanandam, A., Hu, B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.003 · Cited by 716 · cited 1× · see citing works
“…Tead cooperation with AP1 transcription factors to coordinate target gene transcription in cancer (55) and show strong potential of combined targeting of the Hippo and MAPK pathways in KRAS-dependent tumors while YAP activation was shown as resistance mechanisms to MAPK inhibition (56, 57).”
BackgroundBinding of Ras to Phosphoinositide 3-Kinase p110α Is Required for Ras- Driven Tumorigenesis in Mice
Gupta, S., Ramjaun, A. R., Haiko, P., Wang, Y., Warne, P. H., Nicke, B., Nye, E. L., Stamp, G., Alitalo, K. K., & Downward, J. (2007) · Cell · doi:10.1016/j.cell.2007.03.051 · Cited by 589 · see citing works
The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies
Lin, L., Sabnis, A. J., Chan, E., Olivas, V., Cade, L., Pazarentzos, E., Asthana, S., Neel, D., Yan, J. J., Lu, X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3218 · Cited by 551 · see citing works
Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition
Xue, J. Y., Zhao, Y., Aronowitz, J., Mai, T. T., Vides, A., Qeriqi, B., Kim, D., Li, C., de Stanchina, E., Mazutis, L., et al. (2020) · Nature · doi:10.1038/s41586-019-1884-x · Cited by 543 · see citing works
Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition
Ryan, M. B., Fece de la Cruz, F., Phat, S., Myers, D. T., Wong, E., Shahzade, H. A., Hong, C. B., & Corcoran, R. B. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-3523 · Cited by 496 · see citing works
Guagnano, V., Furet, P., Spanka, C., Bordas, V., Douget, M. L., Stamm, C., Brueggen, J., Jensen, M. R., Schnell, C., SCHMID, H. A., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2006222 · Cited by 485 · see citing works
PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers
Wee, S., Jagani, Z., Xiang, K. X., Loo, A., Dorsch, M., Yao, Y.-M., Sellers, W. R., Lengauer, C., & Stegmeier, F. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4765 · Cited by 455 · see citing works
MED12 Controls the Response to Multiple Cancer Drugs through Regulation of TGF-β Receptor Signaling
Huang, S., Hölzel, M., Knijnenburg, T., Schlicker, A., Roepman, P., McDermott, U., Garnett, M., Grernrum, W., Sun, C., Prahallad, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.035 · Cited by 430 · see citing works
Self-citationA combinatorial strategy for treating KRAS-mutant lung cancer
Manchado, E., Weissmueller, S., Morris, J. P., Chen, C.-C., Wullenkord, R., Lujambio, A., de Stanchina, E., Poirier, J. T., Gainor, J. F., Corcoran, R. B., et al. (2016) · Nature · doi:10.1038/nature18600 · Cited by 403 · see citing works
A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
Whittaker, S. R., Theurillat, J.-P. P., Allen, E. M. V., Wagle, N., Hsiao, J., Cowley, G. S., Schadendorf, D., Root, D. E., & Garraway, L. A. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0470 · Cited by 360 · see citing works
Single-Agent Divarasib (GDC-6036) in Solid Tumors with a <i>KRAS</i> G12C Mutation
Sacher, A., LoRusso, P., Patel, M. R., Miller, W. H., Garralda, E., Forster, M. D., Santoro, A., Falcon, A., Kim, T. W., Paz-Ares, L., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2303810 · Cited by 328 · see citing works
Galan-Cobo, A., Sitthideatphaiboon, P., Qu, X., Poteete, A., Pisegna, M. A., Tong, P., Chen, P.-H., Boroughs, L. K., Rodriguez, M. L. M., Zhang, W., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3527 · Cited by 292 · see citing works
SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
Fedele, C., Li, S., Teng, K. W., Foster, C. J. R., Peng, D., Ran, H., Mita, P., Geer, M. J., Hattori, T., Koide, A., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201414 · Cited by 265 · see citing works
Self-citationKRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition
Misale, S., Fatherree, J. P., Cortez, E., Li, C., Bilton, S., Timonina, D., Myers, D. T., Lee, D., Gomez-Caraballo, M., Greenberg, M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0368 · Cited by 259 · see citing works
Multiple Requirements for SHPTP2 in Epidermal Growth Factor-Mediated Cell Cycle Progression
Bennett, A. M., Hausdorff, S. F., O’Reilly, A. M., Freeman, R. M., & Neel, B. G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1189 · Cited by 246 · see citing works
Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer
LaMarche, M. J., Acker, M., Argintaru, A., Bauer, D., Boisclair, J., Chan, H., Chen, C. H.-T., Chen, Y.-N., Chen, Z., Deng, Z., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01170 · Cited by 231 · see citing works
Wang, T., Maierhofer, C., Speicher, M. R., Christoph Lengauer, C., Vogelstein, B., Kinzler, K. W., & Velculescu, V. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202610899 · Cited by 223 · see citing works
GTPase activating proteins: critical regulators of intracellular signaling
Donovan, S., Shannon, K., & Bollag, G. E. (2002) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(01)00041-5 · Cited by 215 · see citing works
Ahmed, T. A., Adamopoulos, C., Karoulia, Z., Wu, X., Sachidanandam, R., Aaronson, S. A., & Poulikakos, P. I. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.013 · Cited by 214 · see citing works
Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer
Molina-Arcas, M., Moore, C., Rana, S., van Maldegem, F., Mugarza, E., Romero-Clavijo, P., Herbert, E., Horswell, S., Li, L.-S., Janes, M. R., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw7999 · Cited by 203 · see citing works
Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC
Negrao, M. V., Araujo, H. A., Lamberti, G., Cooper, A. J., Akhave, N. S., Zhou, T., Delasos, L., Hicks, J. K., Aldea, M., Minuti, G., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1420 · Cited by 203 · see citing works
Requirement for Interaction of PI3-Kinase p110α with RAS in Lung Tumor Maintenance
Castellano, E., Sheridan, C., Thin, M. Z., Nye, E. L., Spencer‐Dene, B., Diefenbacher, M. E., Moore, C., Kumar, M. S., Murillo, M. M., Gronroos, E. C., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.012 · Cited by 184 · see citing works
KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy
Ryan, M. B., Coker, O., Sorokin, A., Fella, K., Barnes, H., Wong, E., Kanikarla, P., Gao, F., Zhang, Y., Zhou, L., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110993 · Cited by 177 · see citing works
KRAS <sup>G12C</sup> inhibition produces a driver-limited state revealing collateral dependencies
Lou, K., Steri, V., Ge, A. Y., Hwang, Y. C., Yogodzinski, C. H., Shkedi, A. R., Choi, A. L. M., Mitchell, D. C., Swaney, D. L., Hann, B., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aaw9450 · Cited by 175 · see citing works
KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer
Krall, E. B., Wang, B., Munoz, D. M., Ilic, N., Raghavan, S., Niederst, M. J., Yu, K., Ruddy, D. A., Aguirre, A. J., Kim, J. W., et al. (2017) · eLife · doi:10.7554/elife.18970 · Cited by 160 · see citing works
Self-citationWeiss, A., Lorthiois, E., Barys, L., Beyer, K. S., Bomio-Confaglia, C., Burks, H., Chen, X., Cui, X., de Kanter, R., Dharmarajan, L., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0158 · Cited by 150 · see citing works
Self-citationMolecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Yaeger, R., Mezzadra, R., Sinopoli, J., Bian, Y., Marasco, M., Kaplun, E., Gao, Y., Zhao, H., Paula, A. D. C., Zhu, Y., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0405 · Cited by 144 · see citing works
ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition
Wang, B., Krall, E. B., Aguirre, A. J., Kim, M., Widlund, H. R., Doshi, M. B., Sicińska, E., Sulahian, R., Goodale, A. B., Cowley, G. S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.031 · Cited by 125 · see citing works
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 · see citing works
Self-citationThe 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 · see citing works
Rapid idiosyncratic mechanisms of clinical resistance to KRAS G12C inhibition
Tsai, Y. S., Woodcock, M. G., Azam, S. H., Thorne, L. B., Kanchi, K. L., Parker, J. S., Vincent, B. G., & Pecot, C. V. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155523 · Cited by 103 · see citing works
Rapid idiosyncratic mechanisms of clinical resistance to KRAS G12C inhibition
Tsai, Y., Woodcock, M. G., Azam, S. H., Thorne, L. B., Kanchi, K., Parker, J. S., Vincent, B. G., & Pecot, C. V. (2022) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 87 · see citing works
Genome-wide CRISPR screening reveals genetic modifiers of mutant EGFR dependence in human NSCLC
Zeng, H., Castillo-Cabrera, J., Manser, M., Lu, B., Yang, Z., Strande, V., Begue, D., Zamponi, R., Qiu, S., Sigoillot, F., et al. (2019) · eLife · doi:10.7554/elife.50223 · Cited by 57 · see citing works
Lu, H., Liu, C., Huynh, H. T., Le, T. B. U., LaMarche, M. J., Mohseni, M., Engelman, J. A., Hammerman, P. S., Caponigro, G., & Hao, H.-X. (2020) · Oncotarget · doi:10.18632/oncotarget.27435 · Cited by 45 · see citing works
The Hippo effector YAP regulates the response of cancer cells to MAPK pathway inhibitors
Lin, L., & Bivona, T. G. (2015) · Molecular & Cellular Oncology · doi:10.1080/23723556.2015.1021441 · Cited by 36 · see citing works
Rago, F., DiMare, M. T., Elliott, G., Ruddy, D. A., Sovath, S., Kerr, G., Bhang, H. C., & Jagani, Z. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.09.009 · Cited by 35 · see citing works
Self-citationEscaping KRAS: Gaining Autonomy and Resistance to KRAS Inhibition in KRAS Mutant Cancers
Adachi, Y., Kimura, R., Hirade, K., & Ebi, H. (2021) · Cancers · doi:10.3390/cancers13205081 · Cited by 28 · see citing works
Dafflon, C., Gaulis, S., Barys, L., Kapur, K., Cornacchione, V., Schukur, L., Bergling, S., Traggiai, E., Jansky, S., Hellmann, L., et al. (2020) · Oncotarget · doi:10.18632/oncotarget.27493 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Takeda, M., Yoshida, S., Inoue, T., Sekido, Y., Hata, T., Hamabe, A., Ogino, T., Miyoshi, N., Uemura, M., Yamamoto, H., et al. (2025) · Cancers · doi:10.3390/cancers17030428 · Cited by 82 · see citing works
- Authors
- Prahallad, A., Weiss, A., Voshol, H., Kerr, G., Sprouffske, K., Yuan, T., Ruddy, D., Meistertzheim, M., Kazic-Legueux, M., Kottarathil, T., Piquet, M., Cao, Y., Martinuzzi-Duboc, L., Buhles, A., Adler, F., Mannino, S., Tordella, L., Sansregret, L., Maira, S.-M., Graus Porta, D., Fedele, C., & Brachmann, S. M.
- Affiliations
- Novartis (Switzerland) (CH)
- 1Novartis Institutes for BioMedical Research, Basel, Switzerland.
- 2Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
- Corresponding author
- Brachmann, Saskia M.
- ORCID
- Prahallad, Anirudh
- Weiss, Andreas
- Voshol, Hans
- Kerr, Grainne
- Sprouffske, Kathleen
- Yuan, Tina
- Ruddy, David
- Meistertzheim, Morgane
- Kazic-Legueux, Malika
- Kottarathil, Tina
- Piquet, Michelle
- Cao, Yichen
- Martinuzzi-Duboc, Laetitia
- Buhles, Alexandra
- Adler, Flavia
- Mannino, Salvatore
- Tordella, Luca
- Sansregret, Laurent
- Maira, Sauveur-Michel
- Graus Porta, Diana
- Fedele, Carmine
- Brachmann, Saskia M.
- Venue
- Cancer Research
- Published
- 2023-11-07
- Volume
- 83
- Issue
- 24
- Pages
- 4130-4141
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC10722132
- OpenAlex
- W4388464575
- Cited by
- 30
- References
- 59
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 7 · 2023: 1
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Research (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Novartis Pharmaceuticals Corporation (n/a)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- KRAS G12C inhibitors, SHP2 inhibitors, non-small cell lung cancer, drug resistance mechanisms, TNO155, alpelisib, ribociclib, PTEN loss, PI3K/mTOR pathway, combination therapy, adaptive resistance, CRISPR screen
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Enzyme Inhibitors, Humans, Lung Neoplasms, Mutation, Pyrazoles, Proto-Oncogene Proteins p21(ras), Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Protein Kinase Inhibitors, Early Detection of Cancer, Clustered Regularly Interspaced Short Palindromic Repeats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
