The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition
Open accessAbstract
The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ovarian adenocarcinomas2–4. KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS–GTP levels. Here we demonstrate that inhibition of the guanine-exchange factors SOS1 and SOS2 or the protein tyrosine phosphatase SHP2 can attenuate this adaptive process and that targeting these factors, both genetically and pharmacologically, can enhance the sensitivity of KRAS-amplified models to MEK inhibition in both in vitro and in vivo settings. These data demonstrate the relevance of copy-number amplification as a mechanism of KRAS activation, and uncover the therapeutic potential for targeting of these tumors through combined SHP2 and MEK inhibition. Amplification of wild-type KRAS in a subset of gastroesophageal tumors drives intrinsic resistance to MAPK inhibition that can be overcome by combined targeting of MEK and SHP2.
Overview
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
Verification
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?
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
“Indeed, inhibition of SHP2 was recently shown to overcome RTK-driven adaptive feedback mechanisms to MEK inhibition, and enhance the efficacy of MEK inhibitor induced growth suppression in vitro and in vivo in RAS-driven cancers (27,41–44).”
From Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition (2020) · cites this paper as [44]
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
“the inhibition of SHP2, which connects RTKs to the RAS signaling pathway and is particularly vulnerable in cancer cells with genetic alteration in KRAS, has attracted considerable attention (12, 56–59).”
From YAP/TAZ mediates resistance to KRAS inhibitors through inhibiting proapoptosis and activating the SLC7A5/mTOR axis (2024) · cites this paper as [59]
Experimental — accuracy not yet measuredIn the citing paper
“Previous experiences with trametinib, a clinical MEK inhibitor have taught us that targeted inhibition of Ras downstream effectors, including MEK would inevitably trigger the relief of ERK-mediated feedback inhibition of RTK signaling, which results in adaptive Ras reactivation that heavily depends on SHP2.86”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [86]
In the citing paper
“In these regards, SHP2 was purposed as a combinatorial target in overcoming the resistance to MEK inhibition and presumably for drugs targeting K-RasG12C.32,86,87”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [86]
In the citing paper
“These findings echo prior studies showing that inhibition of RTK-driven feedback reactivation with SHP2 inhibitors can improve the response to MEK inhibitors [107,108,109].”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [109]
In the citing paper
“Recent studies in KRAS-mutant lung cancer (54, 55) and pancreatic adenocarcinoma (55), KRAS-amplified gastric carcinoma (56), and multiple other cancer models expressing mutant or wild-type KRAS (57, 58) revealed that the anti-tumor effect of MEK inhibitor treatment could be dramatically potentiated by concurrent SHP2 inhibition.”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Comprehensive molecular characterization of gastric adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13480 · Cited by 6,498
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
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 · cited 1×
“SHP099, a potent and selective allosteric inhibitor to the catalytic site of SHP2, was recently developed 20,21 .”
Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?
Vigil, D., Cherfils, J., Rossman, K. L., & Der, C. J. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2960 · Cited by 850
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
In vitro expansion and genetic modification of gastrointestinal stem cells in spheroid culture
Miyoshi, H., & Stappenbeck, T. S. (2013) · Nature Protocols · doi:10.1038/nprot.2013.153 · Cited by 739
Dulak, A. M., Stojanov, P., Peng, S., Lawrence, M. S., Fox, C., Stewart, C., Bandla, S., Imamura, Y., Schumacher, S. E., Shefler, E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2591 · Cited by 736
Self-citationRas history: The saga continues
Cox, A. D., & Der, C. J. (2010) · Small GTPases · doi:10.4161/sgtp.1.1.12178 · Cited by 706
Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism
Lito, P., Solomon, M., Li, L.-S., Hansen, R., & Rosen, N. (2016) · Science · doi:10.1126/science.aad6204 · Cited by 691
Cited by
Sorted by citations
Items 201–279 of 279
Baltanás, F. C., Kramer‐Drauberg, M., García‐Navas, R., Patrucco, E., Petrini, E., Arnhof, H., Juan, A. O.-S., Rodríguez-Ramos, P., Borrajo, J., Calzada, N., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.18.613686 · Cited by 4
Targeting Esophageal Cancer: Promising Drugs for the Clinical Landscape and Key Knowledge Gaps
Akumaga, T., Park, H., Lockhart, A. C., & Jin, R. U. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s543686 · Cited by 3
Zhang, Z., Zhang, K., Liao, X., Yuan, Q., & Zhang, H. (2024) · iScience · doi:10.1016/j.isci.2024.109859 · Cited by 3
Oncology Combination Dose‐Finding Study Design for Targeted and Immuno‐Oncology Therapies
Zhou, L., Reddy, M. B., Mittapalli, R. K., Yang, J., & Yin, D. (2023) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3085 · Cited by 3
Drugging the undruggable: Advances in targeting KRAS signaling in solid tumors
Tripathi, P., Kumari, R., & Pathak, R. (2024) · International review of cytology · doi:10.1016/bs.ircmb.2023.11.004 · Cited by 3
Zhou, H., Li, G., Kan, L., Yang, M., Liu, Y., Miu, X., Shi, L., Yang, Z., Zheng, X., Chen, H., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e30475 · Cited by 3
Choi, D.-H., Jang, H., Lim, S. H., Kim, S. T., Hong, J. Y., Park, S. H., Park, J. O., Kim, D. G., Kim, K., & Lee, J. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155473 · Cited by 3
Wang, S. C., Yeu, Y., Hammer, S. T. G., Xiao, S., Zhu, M., Hong, C., Yoon, L. Y., Nassour, I., Shen, J., Agarwal, D., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/764779 · Cited by 3
Wang, Y., Liao, Y., Sun, Y., Mitra, B., Guo, R., Piedras, B. I., White, S., Tang, H.-Y., Asara, J. M., Tempera, I., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-65760-6 · Cited by 7
Sailo, B. L., Vishwa, R., Girisa, S., Aswani, B. S., Abbas, M., Alqahtani, M. S., Almubarak, H. A., Hegde, M., & Kunnumakkara, A. B. (2025) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266319955241224073611 · Cited by 2
Song, Y., Ren, X., Yang, X., Xiong, J., Wang, W., Tang, K., & Yu, B. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00524 · Cited by 3
Darmadi, D., Aghazadeh-Habashi, K., Ayvazyan, S. R., Bozorgnia, A., & Khodabandehloo, E. (2025) · Discover Oncology · doi:10.1007/s12672-025-03843-y · Cited by 2
Clerici, S. P., Oliveira, P. F. D. S., Akagi, E. M., Cordeiro, H. G., Azevedo-Martins, J. M., Faria, A. V. D. S., & Ferreira‐Halder, C. V. (2021) · Biological Chemistry · doi:10.1515/hsz-2020-0355 · Cited by 2
Sahu, P., Mitra, A., & Ganguly, A. (2024) · International review of cytology · doi:10.1016/bs.ircmb.2024.01.005 · Cited by 2
Molecular and Clinicopathological Correlates of Wild-Type KRAS Expression in Prostate Cancer
Ebili, H. O., Omenai, S. A., Ezenkwa, U. S., Ale, A. O., Akintola, P. A., Adetona, A. E., Akunwata, C. U., Mashor, M. I., Nwanji, I. D., Iyapo, O., et al. (2024) · annals of urologic oncology · doi:10.32948/auo.2024.07.29 · Cited by 2
Chen, Q., Liu, Z., Tan, Y., Pan, S., An, W., & Xu, H. (2022) · Cancer Medicine · doi:10.1002/cam4.4861 · Cited by 2
Combined SHP2 and ERK inhibition for the treatment of KRAS-driven Pancreatic Ductal AdenocarcinomaPreprint
Ciecielski, K. J., Mulero‐Sánchez, A., Berninger, A., Cañas, L. R., Bosma, A. R., Görgülü, K., Wu, N., Diakopoulos, K. N., Kaya-Aksoy, E., Ruess, D. A., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.14.472574 · Cited by 2
RAS mutation-specific signaling dynamics in response to paralog- and state- selective RAS inhibitorsPreprint
Baars, B., Orive-Ramos, A., Kou, Z., Gaire, B., Desaunay, M., Adamopoulos, C., Aaronson, S. A., Wang, S., Gavathiotis, E., & Poulikakos, P. I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.14.638317 · Cited by 2
Shao, K., Zhu, H., Lin, X., Liang, Q., Lei, Z., Gao, B., Chen, H., & Zhang, H. (2024) · International Journal of Clinical Oncology · doi:10.1007/s10147-024-02610-3 · Cited by 1
Wakatsuki, T., Yamamoto, N., Ishizuka, N., Hironaka, S., Minashi, K., Kadowaki, S., Hirano, H., Shoji, H., Yamaguchi, T., Chin, K., et al. (2026) · Targeted Oncology · doi:10.1007/s11523-026-01204-5 · Cited by 1
Zhang, Y., Wang, H., Wei, Y., Pan, Y., Song, X., Shao, J., Yu, L., Shi, T., & Wang, Y. (2026) · eLife · doi:10.7554/elife.104060.3 · Cited by 1
Wang, S., Zhao, X., Dong, J. X., Zhang, J., Wang, Y., Jin, H., Jiang, X., Chen, L., Zhang, M., Ji, L., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08477-4 · Cited by 1
Hsu, M.-F., Koike, S., Chen, C.-S., Najjar, S. M., Meng, T., & Haj, F. G. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116590 · Cited by 1
Genomic differences of patients with hematologic malignancies in different age groups
Yang, X., Wang, Q., Sun, Y.-H., Zhang, Z., Wuchty, S., Liang, Z., & Dong, Y. (2024) · Communications Biology · doi:10.1038/s42003-024-07293-0 · Cited by 2
Cooperation between oncogenic NRF2 and wild-type HRAS promotes progression of breast cancer
Kim, S., Saeidi, S., Cho, N., Lee, H., Han, W., Kim, K. P., & Surh, Y. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.111920 · Cited by 1
Pan-cancer organoid validation of tumor outlier chromosomal amplification eventsPreprint
Salahudeen, A. A., Yuki, K., Seoane, J. A., Mah, A. T., Smith, A. R., Kolahi, K. S., Sean de la, O., Hart, D. J., Ding, J., Ma, Z., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.05.463147 · Cited by 1
Sait, S. F., Tang, K.-H., Angus, S. P., Brown, R. M., Sun, D., Xie, X., Iltis, C., Lien, M. C., Socci, N. D., Bale, T., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.18.504317 · Cited by 1
SHP2 binds directly to SOS1 to enable RAS activationPreprint
Araki, T., Agrawal, Y., Katti, S. S., Nguyen, H. L. D., Yeggoni, D. P., Geer, M. J., Wei, W., Woutersen, D. T. J., Bijlsma, T., Lian, C. G., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.12.731952 · Cited by 3
Self-citationMolecularly Targeted Therapy for Patients with BRAF Wild-Type Melanoma
Chandra, S., McArthur, G., & Sosman, J. (2019) · Cutaneous Melanoma · doi:10.1007/978-3-319-46029-1_55-1
Zhou, L., Lu, H., Xin, L., Zhou, Q., Wu, Y., Li, S., & Yuan, Y. (2020) · Research Square · doi:10.21203/rs.3.rs-117996/v1
Recent updates of therapeutic strategy of esophagogastric junction adenocarcinoma
Maruyama, S., Imamura, Y., Kanie, Y., Sakamoto, K., Fujiwara, D., Okamura, A., Kanamori, J., & Watanabe, M. (2021) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2021.113
Self-citationImproving cancer therapy through unconventional strategies
Neto, J. M. F. (2021) · Utrecht University Repository (Utrecht University) · doi:10.33540/1009
Construction and Validation of a Protein-associated Prognostic Model for Gastrointestinal Cancer
Miao, Y., Mi, D., Mu, L., Chen, Y., Tang, X., Wang, J., & Quan, W. (2022) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207325666220414105743
Molecularly Targeted Therapy for Patients with BRAF Wild-Type Melanoma
Chandra, S., McArthur, G. A., & Sosman, J. A. (2020) · Springer eBooks · doi:10.1007/978-3-030-05070-2_55
Younesian, O., Jafari, S. M., Arabi, M. S., Naseh, H., Hosseinzadeh, S., & Joshaghani, H. (2023) · Research Square · doi:10.21203/rs.3.rs-2442558/v1
Data from Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition
Ryan, M. B., de la Cruz, F. F., Phat, S., Myers, D. T., Wong, E., Shahzade, H. A., Hong, C. B., & Corcoran, R. B. (2023) · doi:10.1158/1078-0432.c.6529850.v1
Sihag, S., Nussenzweig, S. C., Walch, H. S., Hsu, M., Tan, K. S., Sánchez-Vega, F., Chatila, W. K., Torre, S. A. D. L., Patel, A., Janjigian, Y. Y., et al. (2023) · doi:10.1158/1078-0432.c.6529997.v1
Data from Vertical Pathway Inhibition Overcomes Adaptive Feedback Resistance to KRASG12C Inhibition
Ryan, M. B., de la Cruz, F. F., Phat, S., Myers, D. T., Wong, E., Shahzade, H. A., Hong, C. B., & Corcoran, R. B. (2023) · doi:10.1158/1078-0432.c.6529850
Qiu, X., Pan, T., Shen, Y., Kuang, T., Zheng, Y., Geng, H., Aimaiti, M., Ni, B., Xia, X., Zhu, C., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4644577
Anand, A., Schömig, L. R., Lange, S., Tran, L., Flisikowski, K., Öllinger, R., Rad, R., Vieth, M. W., Steiger, K., Baumeister, T., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.07.592904
Zhang, Y., Wang, H., Wei, Y., Pan, Y., Song, X., Shi, T., Shao, J., Yu, L., Liu, B., Wang, Y., et al. (2025) · eLife · doi:10.7554/elife.104060.1
Zhang, Y., Wang, H., Wei, Y., Pan, Y., Song, X., Shao, J., Yu, L., Shi, T., & Wang, Y. (2025) · eLife · doi:10.7554/elife.104060
Emmet, M., Mehta, A., & Klempner, S. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-800684-9.00009-5
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732491
Additional file 1 of Clinically conserved genomic subtypes of gastric adenocarcinoma
Jeong, Y. S., Eun, Y.-G., Lee, S. H., Kang, S.-H., Yim, S. Y., Kim, E. H., Noh, J. K., Sohn, B. H., Woo, S. R., Kong, M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24098139
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26019718
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732494
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732482
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732476
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732479
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732497
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732485
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732488
Yuan, Q., Wang, R., Li, X., Sun, F., Lin, J., Fu, Z., & Zhang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26707077
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26019632
Yuan, Q., Wang, R., Li, X., Sun, F., Lin, J., Fu, Z., & Zhang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26707074
Kaneko, S., Takasawa, K., Asada, K., Shiraishi, K., Ikawa, N., Machino, H., Shinkai, N., Matsuda, M., Masuda, M., Adachi, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26732473
Zhang, Y., Wang, H., Wei, Y., Pan, Y., Song, X., Shao, J., Yu, L., Shi, T., & Wang, Y. (2026) · eLife · doi:10.7554/elife.104060.2
Yin, J., Rixiati, Y., Xu, Y., Yang, P., Sheng, C., & Wang, Z. (2026) · npj Precision Oncology · doi:10.1038/s41698-026-01380-7
Impact de la protéine SHP2 associé au syndrome de Noonan sur le métabolisme glucidique
Paccoud, R. (2018) · theses.fr (ABES) · doi:10.70675/f9b9b046zdf4bz404fz9689z8deb20f6e5ac
NSUN5–CBX8 m5C axis promotes gastric tumorigenesis by activating JAK–STAT3 signaling
Yin, J., Li, L., Niu, Y., Wang, Q., Liu, W., Gu, Y., Wang, X., & Huang, L. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112563
Li, R., Long, L., Zhu, R., Wu, C., & Zhang, J. (2026) · 中国科学基金 · doi:10.3724/bnsfc-2025.05.14.0002
Liu, X., Xiao, Y., Zhou, Y., Teng, Y., Zou, J., Zhou, Y., Fan, X., Zhao, J., Qiu, J., Tang, L., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00196
Kızıl, H. E., Ekíncíoğlu, Y., Özkan, E. H., Güllü, E., & Nartop, D. (2026) · Discover Chemistry. · doi:10.1007/s44371-026-00785-4
Wang, Y., Xia, J., Ding, H., & Li, D. (2026) · Pharmaceutical Science Advances · doi:10.1016/j.pscia.2026.100128
Wang, K., Liu, Y., Zhang, Z., Hu, Y., Zhong, Y., Jiang, S., Zhang, X., Zhang, K., & Wang, T. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00353
Zein, R. A., Kawaf, R. R., Ramadan, W. S. H., Ghemrawi, R., Harati, R., El‐Awady, R., & Khoder, G. (2026) · Microbiological Research · doi:10.1016/j.micres.2026.128632
Salih, R., Sirajudeen, F., & Rahmani, M. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.08.030
Bharti, J., Gogu, P., Sarwan, D. N., Pathak, M. K., Gupta, P. S., Dwivedi, A. R., & Pathak, P. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118379
Chen, Y.-L., Chen, W.-C., Yeh, T., Ho, H.-H., Chen, T.-C., & Wang, W. (2026) · Biomedical Journal · doi:10.1016/j.bj.2026.101036
Anand, A., Schömig, L. R., Klaas, L., Glosch, A.-K., Proaño-Vasco, A., Borgmann, M., Khiat, M., Kuznetsov, A., Patel, V. B., Ritzkowski, C., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-71355-y
BindingDB Entry 50023110: Discovery of Small Molecules that Bind to Son of Sevenless 2 (SOS2).
BindingDB (2026) · UC San Diego · doi:10.7270/q2hh6qxh
BindingDB Entry 50009588: Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors.
BindingDB (2021) · UC San Diego · doi:10.7270/q25t3pzd
BindingDB Entry 50022804: Advances in SHP2 tunnel allosteric inhibitors and bifunctional molecules.
BindingDB (2026) · UC San Diego · doi:10.7270/q2v98dw4
Metadata
- Authors
- Wong, G. S., Zhou, J., Liu, J. B., Wu, Z., Xu, X., Li, T., Xu, D., Schumacher, S. E., Puschhof, J., McFarland, J., Zou, C., Dulak, A., Henderson, L., Xu, P., O’Day, E., Rendak, R., Liao, W.-L., Cecchi, F., Hembrough, T., Schwartz, S., Szeto, C., Rustgi, A. K., Wong, K.-K., Diehl, J. A., Jensen, K., Graziano, F., Ruzzo, A., Fereshetian, S., Mertins, P., Carr, S. A., Beroukhim, R., Nakamura, K., Oki, E., Watanabe, M., Baba, H., Imamura, Y., Catenacci, D., & Bass, A. J.
- Affiliations
- Dana-Farber Cancer Institute (US)
- University of Chicago Medical Center (US)
- Broad Institute (US)
- OncoPlex Diagnostics (United States) (US)
- Abramson Cancer Center (US)
- Harvard University (US)
- Medical University of South Carolina (US)
- University of Illinois Urbana-Champaign (US)
- University of Urbino (IT)
- Kumamoto University (JP)
- Kyushu University (JP)
- The Cancer Institute Hospital (JP)
- Corresponding author
- Catenacci, Daniel
- Bass, Adam J.
- ORCID
- Zhou, Jin
- Wu, Zhong
- Li, Tianxia
- Schumacher, Steven E.
- Puschhof, Jens
- McFarland, James
- Zou, Charles
- Dulak, Austin
- Henderson, Les
- Xu, Peng
- O’Day, Emily
- Hembrough, Todd
- Schwartz, Sarit
- Szeto, Christopher
- Rustgi, Anil K.
- Wong, Kwok-Kin
- Diehl, J. Alan
- Jensen, Karin
- Graziano, Francesco
- Ruzzo, Annamaria
- Fereshetian, Shaunt
- Mertins, Philipp
- Carr, Steven A.
- Beroukhim, Rameen
- Nakamura, Kenichi
- Oki, Eiji
- Watanabe, Masayuki
- Baba, Hideo
- Imamura, Yu
- Catenacci, Daniel
- Bass, Adam J.
- Venue
- Nature Medicine
- Published
- 2018-05-28
- Volume
- 24
- Issue
- 7
- Pages
- 968-977
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6039276
- OpenAlex
- W2804957989
- Semantic Scholar
- 6af671acbd44534590b63fcb147e769f8ce02fc2
- Cited by
- 266
- References
- 48
- Citations by year
- 2026: 22 · 2025: 20 · 2024: 41 · 2023: 24 · 2022: 32 · 2021: 46 · 2020: 36 · 2019: 36 · 2018: 9
- FWCI
- 11.18
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-08-09)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Society for the Promotion of Science (16H06259)
- National Cancer Institute (P50CA127003, P01CA098101, K23CA178203, P30CA014599)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- gastroesophageal cancer, gastric cancer, esophageal adenocarcinoma, MEK inhibition, SHP2 inhibition, SOS1, SOS2, MAPK signaling, MAPK inhibitor resistance, combination therapy, guanine nucleotide exchange factor, protein tyrosine phosphatase
- MeSH terms
- Animals, Disease Models, Animal, Esophageal Neoplasms, Gene Amplification, Humans, Piperidines, Pyridones, Pyrimidines, Pyrimidinones, Stomach Neoplasms, Proto-Oncogene Proteins p21(ras), Mitogen-Activated Protein Kinase Kinases, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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
