Cited by 106Protein Kinase Regulation and GTPase SignalingLung Cancer Treatments and MutationsMelanoma and MAPK Pathways

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Cell Type–specific Adaptive Signaling Responses to KRASG12C Inhibition

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Solanki, Hitendra S., Welsh, Eric A., Fang, Bin, Izumi, Victoria, Darville, Lancia, Stone, Brandon, Franzese, Ryan, Chavan, Sandip, Kinose, Fumi, Imbody, Denis, Koomen, John M., Rix, Uwe, Haura, Eric B.·2021·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-20-3872PMC PMC9940280

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Abstract

Purpose: Covalent inhibitors of KRASG12C specifically target tumors driven by this form of mutant KRAS, yet early studies show that bypass signaling drives adaptive resistance. Although several combination strategies have been shown to improve efficacy of KRASG12C inhibitors (KRASi), underlying mechanisms and predictive strategies for patient enrichment are less clear. Experimental Design: We performed mass spectrometry–based phosphoproteomics analysis in KRASG12C cell lines after short-term treatment with ARS-1620. To understand signaling diversity and cell type–specific markers, we compared proteome and phosphoproteomes of KRASG12C cells. Gene expression patterns of KRASG12C cell lines and lung tumor tissues were examined. Results: Our analysis suggests cell type–specific perturbation to ERBB2/3 signaling compensates for repressed ERK and AKT signaling following ARS-1620 treatment in epithelial cell type, and this subtype was also more responsive to coinhibition of SHP2 and SOS1. Conversely, both high basal and feedback activation of FGFR or AXL signaling were identified in mesenchymal cells. Inhibition of FGFR signaling suppressed feedback activation of ERK and mTOR, while AXL inhibition suppressed PI3K pathway. In both cell lines and human lung cancer tissues with KRASG12C, we observed high basal ERBB2/3 associated with epithelial gene signatures, while higher basal FGFR1 and AXL were observed in cells/tumors with mesenchymal gene signatures. Conclusions: Our phosphoproteomic study identified cell type–adaptive responses to KRASi. Markers and targets associated with ERBB2/3 signaling in epithelial subtype and with FGFR1/AXL signaling in mesenchymal subtype should be considered in patient enrichment schemes with KRASi.

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Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
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Self-citation
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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 · cited 1×
“The advancements in medicinal chemistry have produced high potency KRAS inhibitors (KRASi), such as ARS-1620, rapid binding to theGDP-bound inactive form, and optimizedpharmacokinetics tomaximize exposure andduration (4, 5).”
Background
Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state
Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759

Show all 50 references

Research works printed but not linked: 1

Jänne PA . A phase 1 clinical trial evaluating the pharmacokinetics (PK), safety, and clinical activity of MRTX849, a mutant-selective small molecule KRAS G12C inhibitor, in advanced solid tumors. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets; 2019 Oct 28; San Diego, CA.

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Wang, L., Wei, D., Li, S., & Jiang, S. (2025) · Discover Oncology · doi:10.1007/s12672-025-03569-x · Cited by 7
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Stern, Y. E., Ghosh, P., Peroza, J., Solanki, H. S., Imbody, D. J., Bridenstine, L., Pandurangan, T., Frydman, S. M., Nickens, K. N., Walker-Mimms, H. L., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-25-0450 · Cited by 7
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Daley, B. R., Sealover, N. E., Sheffels, E., Hughes, J. M., Gerlach, D., Hofmann, M. H., Kostyrko, K., Mair, B., Linke, A. J., Beckley, Z., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.07.570642 · Cited by 7
Differential Response and Resistance to KRAS-Targeted Therapy
Liu, Z., Lenz, H., Yu, J., & Zhang, L. (2025) · Molecular Carcinogenesis · doi:10.1002/mc.23908 · Cited by 7
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Ito, M., Miyata, Y., Hirano, S., Morihara, N., Takemoto, M., Irisuna, F., Kushitani, K., Suda, K., Soh, J., Takeshima, Y., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02187-y · Cited by 6
Novel anti-HER2 nanobody-drug conjugates with enhanced penetration of solid tumor and BBB, reduced systemic exposure and superior antitumor efficacy
Wang, Y., Liu, L., Yang, Q., & Yu, K. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01634-3 · Cited by 6
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Shin, D. H., Choi, M., Han, C., & Kim, S. S. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-025-01536-8 · Cited by 7
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Sealover, N. E., Finniff, B. A., Hughes, J. M., Sheffels, E., Lee, H., LaMorte, J. P., Gambhir, V., Beckley, Z., Linke, A. J., Wilkerson, M. D., et al. (2025) · Science Signaling · doi:10.1126/scisignal.adx5186 · Cited by 7
Combinatorial approaches for mitigating resistance to KRAS-targeted therapies
Warren, H. R., Ross, S. J., Smith, P. D., Coulson, J. M., & Prior, I. A. (2022) · Biochemical Journal · doi:10.1042/bcj20220440 · Cited by 6
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Lin, Q., Morales-Giron, A. A., Sander, C., Curtis, J. M., Barnes, H., Patel, P. S., de la Cruz, F. F., Riedl, J. M., Matsubara, H., Nakamura, H., et al. (2026) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-25-1788 · Cited by 6
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Pandey, G., Mazzacurati, L., Rowsell, T. M., Horvat, N. P., Amin, N. E., Zhang, G., Akuffo, A. A., Colin, C., Haura, E. B., Kuykendall, A. T., et al. (2024) · American Journal of Hematology · doi:10.1002/ajh.27282 · Cited by 6
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Sweet-Cordero, A., Marini, K. D., Champion, E. C., Lee, A. G., Young, I., Leung, S. G., Mathey‐Andrews, N., Jacks, T., Jackson, P. K., & Cochran, J. R. (2024) · Research Square · doi:10.21203/rs.3.rs-4046823/v1 · Cited by 5
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Abdollahi, A., Favata, M. F., Weber, M., Roman, V. D., Hess, R., Hammond, K., Farren, M. R., Schaffer, M., Gilmartin, A. G., Wang, H., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0327588 · Cited by 3
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Dcunha, L., Edakkad, B., John, L., Shivamurthy, P. B., Bera, P., Das, D., Raju, R., Balaya, R. D. A., & Kanekar, S. (2026) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2026.141141 · Cited by 3
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Rosen, J. C., Cao, P. M., Pham, N., Waas, M., Li, Q., Hueniken, K., Wang, M., Navab, R., Wybenga-Groot, L. E., Radulovich, N., et al. (2025) · British Journal of Cancer · doi:10.1038/s41416-025-03216-w · Cited by 2
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Patel, H. V., Smith, A. E., Chan, S., Gasendo, J. G., Jombik, A., Greer, J. E., Samantaray, T., Kessler, L. V., Mitra, A., Zhu, X., et al. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-2764 · Cited by 3
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Khusnutdinov, R. (2024) · Reviews and Advances in Chemistry · doi:10.1134/s2634827624600312 · Cited by 2
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Herbst, S. A., & White, F. M. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100483 · Cited by 2
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Gargalionis, A. N., Papavassiliou, K. A., & Papavassiliou, A. G. (2025) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2025.03.009 · Cited by 1
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Luo, X., Zhou, F., Tang, Y., Liu, X., Xiao, R., Gu, M., Bai, J., Jiang, D., Yang, G., You, L., et al. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003776 · Cited by 2
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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
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Nadal, E., Ambrogio, C., Santamarı́a, D., & Lindsay, C. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21861-3.00018-8 · Cited by 2
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Alem, D., Yang, X., Beato, F., Sarcar, B., Tassielli, A. F., Dai, R., Hogenson, T. L., Park, M. A., Jiang, K., Cai, J., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.14.512156 · Cited by 1
The farnesyl transferase inhibitor KO-2806 re-sensitizes relapsing tumors to RAS inhibitionPreprint
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Udagawa, H., Shibata, Y., Nilsson, M. B., Nishii, K., Robichaux, J. P., Galan-Cobo, A., He, J., Poteete, A., Qian, Y., Molkentine, D., et al. (2026) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2026.103991 · Cited by 1
A Gold Standard-Derived Modular Barcoding Approach to Cancer Transcriptomics
Zhu, Y., Koleilat, M. K., Roszik, J., Kwong, M. K., Wang, Z., Maru, D. M., Kopetz, S., & Kwong, L. N. (2024) · Cancers · doi:10.3390/cancers16101886
Leveraging death of drug-sensitive cancer cells to promote immune-mediated bystander killing of subclones of drug-resistant tumour cellsPreprint
Tomaschko, M., Ng, K., Moore, C., Pillsbury, C. E., Rana, S., Campbell, J., Mukherjee, S., Mikolajczak, A., Anastasiou, P., de Castro, A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.27.684825
Blockade of the KRAS-FOSL1 axis elicits DNA damage repair deficiency exploitable with local and systemic genotoxic therapiesPreprint
Vicent, S., Welch, C., Novoa, G., Vasquez-Valencia, C., Macaya, I., Jimenez-Alonso, J. J., Subrizio, A., Lagos, A. F., Llorente, S., Jimenez, M., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9085811/v1
MAPK pathway modulation and its implications in KRAS mutant lung adenocarcinoma
Román, S. D. H. (2023) · theses.fr (ABES) · doi:10.70675/8eaccae1ze96bz4279zb69fzaafa5e50c341
Unlocking drug sensitivity in KRAS
MingCong, L. I., YueSong, Z. H. O. U., Qiao, T. D., QingLin, B. A. I., & Li, C. (2026) · Scientia Sinica Vitae · doi:10.1360/ssv-2025-0279
Non-small cell lung cancer in 2026: A narrative review of clinical advances and systemic challenges
Frey, C. (2026) · Disease and Therapeutics · doi:10.1016/j.dist.2026.100010
Targeting GSTZ1 Sensitizes KRAS G12C -Mutant Lung Cancer Cells by Overcoming Glutathione and Glycolysis Pathway Rewiring
Liao, Y., Li, X., Liu, M., Fernandes, V. C., Duckett, D., Haura, E. B., Monastyrskyi, A., & Rix, U. (2026) · Cancer Research Communications · doi:10.1158/2767-9764.crc-25-0698
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KRAS Inhibitor–Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones
Tomaschko, M., Ng, K., Moore, C. L., Pillsbury, C. E., Rana, S., Campbell, J., Mukherjee, S., Mikolajczak, A., Anastasiou, P., de Castro, A., et al. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-5693
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

Authors: Solanki, H. S., Welsh, E. A., Fang, B., Izumi, V., Darville, L., Stone, B., Franzese, R., Chavan, S., Kinose, F., Imbody, D., Koomen, J. M., Rix, U., & Haura, E. B.
Affiliations: Moffitt Cancer Center (US)
University of South Florida (US)
Corresponding author: Haura, Eric B.
ORCID: Solanki, Hitendra S.
Welsh, Eric A.
Fang, Bin
Izumi, Victoria
Darville, Lancia
Stone, Brandon
Franzese, Ryan
Chavan, Sandip
Kinose, Fumi
Imbody, Denis
Koomen, John M.
Rix, Uwe
Haura, Eric B.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2021-02-22
Volume: 27
Issue: 9
Pages: 2533-2548
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-20-3872
PMC: PMC9940280
OpenAlex: W3130115867
Cited by: 106
References: 50
Citations by year: 2026: 17 · 2025: 25 · 2024: 25 · 2023: 19 · 2022: 10 · 2021: 10
FWCI: 5.02
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: State of Florida Bankhead Coley (5BC07)
H. Lee Moffitt Cancer Center and Research Institute (P30-CA076292)
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, KRAS inhibitors, adaptive resistance, bypass signaling, phosphoproteomics, FGFR1, AXL, SHP2, SOS1, PI3K signaling, mTOR, lung cancer, patient enrichment, combination therapy
MeSH terms: Alleles, Chromatography, Liquid, Humans, Mutation, Phosphoproteins, Piperazines, Quinazolines, Biomarkers, Tumor, Signal Transduction, Proto-Oncogene Proteins p21(ras), Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Computational Biology, Amino Acid Substitution, Receptor, ErbB-3, Protein Interaction Mapping, Proteomics, Cell Line, Tumor, Receptor, Fibroblast Growth Factor, Type 1, Tandem Mass Spectrometry, Epithelial-Mesenchymal Transition, Protein Interaction Maps

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Cell Type–specific Adaptive Signaling Responses to KRASG12C Inhibition

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