Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition
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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.
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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.
“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]
In the copy’s section labeled Abstract (page not provided), SHP2 inhibition blocked adaptive signaling and enhanced MEK-inhibitor growth suppression in vitro and in vivo in KRAS-amplified gastric cancer models. The claim’s broader reference to RAS-driven cancers is not supported by these results: adding SHP2 inhibition did not improve tumor-growth suppression in the KRAS-mutant xenograft model. (LLM, conf=0.88)
Experimental — accuracy not yet measuredInhibition of SHP2 has attracted considerable attention as a combination strategy to enhance antitumor activity of KRAS G12C inhibitors.
“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]
The paper’s Abstract reports that SHP2 inhibition enhanced the antitumor effects of MEK inhibition in wild-type KRAS-amplified gastroesophageal cancer models. It does not establish that SHP2 inhibition enhances KRAS G12C inhibitors; its combination partner was a MEK inhibitor, and the reported benefit was in KRAS-amplified rather than KRAS-mutant models. No page number is available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTargeted inhibition of Ras downstream effectors including MEK inevitably triggers relief of ERK-mediated feedback inhibition of RTK signaling, resulting in adaptive Ras reactivation that heavily depends on SHP2.
“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]
SHP2 was proposed as a combinatorial target for overcoming resistance to MEK inhibition and presumably for drugs targeting K-RasG12C.
“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]
Inhibition of RTK-driven feedback reactivation with SHP2 inhibitors can improve the response to MEK inhibitors.
“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]
Recent studies in KRAS-mutant lung cancer and pancreatic adenocarcinoma, KRAS-amplified gastric carcinoma, and multiple other cancer models revealed that the anti-tumor effect of MEK inhibitor treatment could be dramatically potentiated by concurrent SHP2 inhibition.
“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]
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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 · see citing works
Comprehensive molecular characterization of gastric adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13480 · Cited by 6,498 · see citing works
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 · 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
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 816 · 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
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 · see citing works
Self-citationIn 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 724 · see citing works
Ras history: The saga continues
Cox, A. D., & Der, C. J. (2010) · Small GTPases · doi:10.4161/sgtp.1.1.12178 · Cited by 706 · see citing works
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 · see citing works
Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment.
Zhang, S.-Q., Yang, W., Kontaridis, M. I., Bivona, T., Wen, G., Araki, T., Luo, J.-C., Thompson, J. A., Schraven, B., Philips, M., et al. (2004) · Molecules and Cells · doi:10.1016/s1097-2765(04)00050-4 · Cited by 470 · see citing works
A 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
The molecular functions of Shp2 in the Ras/Mitogen-activated protein kinase (ERK1/2) pathway
Dance, M., Montagner, A., Salles, J.-P., Yart, A., & Raynal, P. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2007.10.002 · Cited by 361 · see citing works
Lito, P., Saborowski, A., Yue, J., Solomon, M., Joseph, E., Gadal, S., Saborowski, M., Kastenhuber, E., Fellmann, C., Ohara, K., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.011 · Cited by 324 · see citing works
Ahronian, L. G., Sennott, E. M., Van Allen, E. M., Wagle, N., Kwak, E. L., Faris, J. E., Godfrey, J. T., Nishimura, K., Lynch, K. D., Mermel, C. H., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1518 · Cited by 322 · see citing works
Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling
Agazie, Y. M., & Hayman, M. J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7875-7886.2003 · Cited by 306 · see citing works
Sun, C., Hobor, S., Bertotti, A., Zecchin, D., Huang, S., Galimi, F., Cottino, F., Prahallad, A., Grernrum, W., Tzani, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.045 · Cited by 304 · see citing works
Garcia Fortanet, J., Chen, C. H.-T., Chen, Y.-N. P., Chen, Z., Deng, Z., Firestone, B., Fekkes, P., Fodor, M., Fortin, P. D., Fridrich, C., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00680 · Cited by 298 · see citing works
Dulak, A. M., Schumacher, S. E., van Lieshout, J., Imamura, Y., Fox, C., Shim, B., Ramos, A. H., Saksena, G., Baca, S. C., Baselga, J. M., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3893 · Cited by 270 · see citing works
Self-citationInhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis
Bunda, S., Burrell, K., Heir, P., Zeng, L., Alamsahebpour, A., Kano, Y., Raught, B., Zhang, Z.-Y., Zadeh, G., & Ohh, M. (2015) · Nature Communications · doi:10.1038/ncomms9859 · Cited by 249 · see citing works
Araki, T., Nawa, H., & Neel, B. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306461200 · Cited by 231 · see citing works
ras gene Amplification and malignant transformation.
Pulciani, S., Santos, E., Long, L. K., Sorrentino, V., & Barbacid, M. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2836 · Cited by 202 · see citing works
KRAS Allelic Imbalance Enhances Fitness and Modulates MAP Kinase Dependence in Cancer
Burgess, M. R., Hwang, E., Mroue, R., Bielski, C. M., Wandler, A. M., Huang, B. J., Firestone, A. J., Young, A., Lacap, J. A., Crocker, L., et al. (2017) · Cell · doi:10.1016/j.cell.2017.01.020 · Cited by 183 · see citing works
Zawistowski, J. S., Bevill, S. M., Goulet, D. R., Stuhlmiller, T. J., Beltran, A. S., Olivares-Quintero, J. F., Singh, D., Sciaky, N., Parker, J. S., Rashid, N. U., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0653 · Cited by 180 · see citing works
Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis
Jeng, H., Taylor, L. J., & Bar‐Sagi, D. (2012) · Nature Communications · doi:10.1038/ncomms2173 · Cited by 176 · see citing works
KRAS gene amplification in colorectal cancer and impact on response to EGFR‐targeted therapy
Valtorta, E., Misale, S., Sartore‐Bianchi, A., Nagtegaal, I. D., Paraf, F., Lauricella, C., Dimartino, V., Hobor, S., Jacobs, B., Ercolani, C., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28106 · Cited by 175 · see citing works
PTPN11 is a central node in intrinsic and acquired resistance to targeted cancer drugs
Prahallad, A., Heynen, G. J. J. E., Germano, G., Willems, S. M., Evers, B., Vecchione, L., Gambino, V., Lieftink, C., Beijersbergen, R. L., Di Nicolantonio, F., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.037 · Cited by 168 · see citing works
Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets
Chen, Y., McGee, J., Chen, X., Doman, T. N., Gong, X., Zhang, Y., Hamm, N., Ma, X., Higgs, R. E., Bhagwat, S. V., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098293 · Cited by 135 · see citing works
Winter, J., Anderson, M., Blades, K., Brassington, C., Breeze, A. L., Chresta, C. M., Embrey, K. J., Fairley, G., Faulder, P., Finlay, M. R. V., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501660t · Cited by 126 · see citing works
Regulation of Ras Signaling Dynamics by Sos-Mediated Positive Feedback
Boykevisch, S., Zhao, C., Sondermann, H., Philippidou, P., Halegoua, S., Kuriyan, J., & Bar‐Sagi, D. (2006) · Current Biology · doi:10.1016/j.cub.2006.09.033 · Cited by 125 · see citing works
Oddo, D., Sennott, E. M., Barault, L., Valtorta, E., Arena, S., Cassingena, A., Filiciotto, G., Marzolla, G., Elez, E., van Geel, R. M. J. M., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0396 · Cited by 121 · see citing works
MEK and PI3K inhibition in solid tumors: rationale and evidence to date
Jokinen, E., & Koivunen, J. P. (2015) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834015571111 · Cited by 116 · see citing works
Maron, S., Alpert, L., Kwak, H., Lomnicki, S., Chase, L. M., Xu, D., O’Day, E., Nagy, R., Lanman, R., Cecchi, F., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1260 · Cited by 116 · see citing works
Self-citationPorfiri, E., & McCormick, F. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5871 · Cited by 110 · see citing works
Catenacci, D. V. T., Henderson, L., Xiao, S., Patel, P. H., Yauch, R. L., Hegde, P. S., Zha, J., Pandita, A., Peterson, A., & Salgia, R. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0175 · Cited by 109 · see citing works
Self-citationDownregulation of the Ras activation pathway by MAP kinase phosphorylation of Sos.
Buday, L., Ph, W., & Downward, J. (1995) · PubMed · Cited by 106 · see citing works
Ras inhibition via direct Ras binding—is there a path forward?
Wang, W., Fang, G., & Rudolph, J. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.07.082 · Cited by 104 · see citing works
Ross, J. S., Ali, S. M., Wang, K., Palmer, G. A., Yelensky, R., Lipson, D., Miller, V. A., Zajchowski, D. A., Shawver, L. K., & Stephens, P. J. (2013) · Gynecologic Oncology · doi:10.1016/j.ygyno.2013.06.019 · Cited by 90 · see citing works
Birkeland, E., Wik, E., Mjøs, S., Høivik, E. A., Trovik, J., Werner, H. M. J., Kusonmano, K., Petersen, K., Raeder, M. B., Holst, F., et al. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.477 · Cited by 84 · see citing works
Activation of RAS family members confers resistance to ROS1 targeting drugs
Cargnelutti, M., Corso, S., Pergolizzi, M., Mévellec, L., Aisner, D. L., Dziadziuszko, R., Varella‐Garcia, M., Comoglio, P. M., Doebele, R. C., Vialard, J. E., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.3311 · Cited by 80 · see citing works
Multiple Decisive Phosphorylation Sites for the Negative Feedback Regulation of SOS1 via ERK*
Kamioka, Y., Yasuda, S., Fujita, Y., Aoki, K., & Matsuda, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.135517 · Cited by 76 · see citing works
Hembrough, T., Thyparambil, S. P., Liao, W.-L., Darfler, M. M., Abdo, J., Bengali, K. M., Hewitt, S. M., Bender, R. A., Krizman, D. B., & Burrows, J. (2013) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2013.03.002 · Cited by 63 · see citing works
Self-citationRational Design of Small Molecule Inhibitors Targeting the Ras GEF, SOS1
Evelyn, C. R., Duan, X., Biesiada, J., Seibel, W. L., Meller, J., & Zheng, Y. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.09.018 · Cited by 63 · see citing works
McNeill, R. S., Canoutas, D. A., Stuhlmiller, T. J., Dhruv, H., Irvin, D., Bash, R., Angus, S. P., Herring, L. E., Simon, J. M., Skinner, K., et al. (2017) · Neuro-Oncology · doi:10.1093/neuonc/nox044 · Cited by 61 · see citing works
Das, K., Gunasegaran, B., Tan, I. B., Deng, N., Lim, K. H., & Tan, P. B. O. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.07.021 · Cited by 55 · see citing works
Catenacci, D. V. T., Liao, W., Thyparambil, S. P., Henderson, L., Xu, P., Zhao, L., Rambo, B., Hart, J. A. L., Xiao, S., Bengali, K. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100586 · Cited by 53 · see citing works
Self-citationras gene Amplification and Malignant Transformation
Pulciani, S., Santos, E., Long, L. K., Sorrentino, V., & Barbacid, M. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2836-2841.1985 · Cited by 51 · see citing works
Tokunaga, R., Imamura, Y., Nakamura, K., Ishimoto, T., Nakagawa, S., Miyake, K., Nakaji, Y., Tsuda, Y., Iwatsuki, M., Baba, Y., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7782 · Cited by 41 · see citing works
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Huang, L., Guo, Z., Wang, F., & Fu, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00780-4 · Cited by 1,127 · see citing works
The current state of the art and future trends in RAS-targeted cancer therapies
Punekar, S. R., Velcheti, V., Neel, B. G., & Wong, K.-K. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00671-9 · Cited by 549 · see citing works
Self-citationVertical 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
Rational combinations of targeted cancer therapies: background, advances and challenges
Jin, H., Wang, L., & Bernards, R. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00615-z · Cited by 503 · see citing works
Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer
Zhu, G., Pei, L., Xia, H., Tang, Q., & Bi, F. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01441-4 · Cited by 482 · see citing works
Hofmann, M. H., Gmachl, M., Ramharter, J., Savarese, F., Gerlach, D., Marszalek, J. R., Sanderson, M. P., Kessler, D., Trapani, F., Arnhof, H., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0142 · Cited by 444 · see citing works
Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants
Hofmann, M. H., Gerlach, D., Misale, S., Petronczki, M., & Kraut, N. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1331 · Cited by 336 · see citing works
SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models
Fedele, C., Ran, H., Diskin, B., Wei, W., Jen, J., Geer, M. J., Araki, K., Ozerdem, U., Simeone, D. M., Miller, G., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0444 · Cited by 315 · 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-citationTargeting KRAS(G12C): From Inhibitory Mechanism to Modulation of Antitumor Effects in Patients
Kim, D., Xue, J. Y., & Lito, P. (2020) · Cell · doi:10.1016/j.cell.2020.09.044 · Cited by 239 · see citing works
Emerging strategies to target RAS signaling in human cancer therapy
Chen, K., Zhang, Y., Qian, L. M., & Wang, P. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01127-w · Cited by 231 · see citing works
Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma
Maron, S. B., Chase, L. M., Lomnicki, S., Kochanny, S. E., Moore, K. L., Joshi, S. S., Landron, S., Johnson, J., Kiedrowski, L. A., Nagy, R. J., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1704 · Cited by 230 · see citing works
Self-citationLee, J., Kim, S. T., Kim, K., Lee, H., Kozarewa, I., Mortimer, P. G. S., Odegaard, J. I., Harrington, E. A., Lee, J.-Y., Lee, T., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0442 · Cited by 230 · see citing works
Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application
Yuan, X., Bu, H., Zhou, J., Yang, C., & Zhang, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00249 · Cited by 224 · see citing works
Self-citationAhmed, 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
The KRAS-G12C inhibitor: activity and resistance
Liu, J., Kang, R., & Tang, D. (2021) · Cancer Gene Therapy · doi:10.1038/s41417-021-00383-9 · Cited by 222 · see citing works
Self-citationEmerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer
Cabanos, H. F., & Hata, A. N. (2021) · Cancers · doi:10.3390/cancers13112666 · Cited by 189 · see citing works
New clinical trial design in precision medicine: discovery, development and direction
Duan, X.-P., Qin, B., Jiao, X., Liu, K., Wang, Z., & Zang, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01760-0 · Cited by 217 · see citing works
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Isermann, T., Sers, C., Der, C. J., & Papke, B. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.11.009 · Cited by 207 · see citing works
SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade
Zhao, M., Guo, W., Wu, Y., Yang, C., Zhong, L., Deng, G., Zhu, Y., Liu, W., Gu, Y., Lu, Y., et al. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2018.08.009 · Cited by 190 · see citing works
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Liu, Q., Qu, J., Zhao, M., Xu, Q., & Sun, Y. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104595 · Cited by 177 · see citing works
Mapping the genomic diaspora of gastric cancer
Yeoh, K. G., & Tan, P. B. O. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00412-7 · Cited by 170 · see citing works
Zhang, H., Schaefer, A., Wang, Y., Hodge, R. G., Blake, D. R., Diehl, J. N., Papageorge, A. G., Stachler, M. D., Liao, J., Zhou, J. R., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0811 · Cited by 166 · see citing works
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Kerr, D. L., Haderk, F., & Bivona, T. G. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2020.11.007 · Cited by 124 · see citing works
A comprehensive review of SHP2 and its role in cancer
Asmamaw, M. D., Shi, X.-J., Zhang, L.-R., & Liu, H.-M. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00698-1 · Cited by 119 · see citing works
Therapeutic targeting of RAS: New hope for drugging the “undruggable”
Khan, I., Rhett, J. M., & O’Bryan, J. P. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.118570 · Cited by 109 · see citing works
Vainonen, J. P., Momeny, M., & Westermarck, J. K. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe2967 · Cited by 105 · see citing works
Combined Inhibition of SHP2 and CXCR1/2 Promotes Antitumor T-cell Response in NSCLC
Tang, K. H., Li, S., Khodadadi-Jamayran, A., Jen, J., Han, H., Guidry, K., Chen, T., Hao, Y., Fedele, C., Zebala, J. A., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0369 · Cited by 105 · see citing works
Self-citationTyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation
Kano, Y., Gebregiworgis, T., Marshall, C. B., Radulovich, N., Poon, B. P. K., St-Germain, J., Cook, J. D., Valencia-Sama, I., Grant, B. M. M., Herrera, S. G., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08115-8 · Cited by 103 · see citing works
Ozkan‐Dagliyan, I., Diehl, J. N., George, S. D., Schaefer, A., Papke, B., Klotz‐Noack, K., Waters, A. M., Goodwin, C. M., Gautam, P., Pierobon, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107764 · Cited by 102 · see citing works
Self-citationDissection of gastric cancer heterogeneity for precision oncology
Ho, S. W. T., & Tan, P. B. O. (2019) · Cancer Science · doi:10.1111/cas.14191 · Cited by 102 · see citing works
Endothelial deletion of SHP2 suppresses tumor angiogenesis and promotes vascular normalization
Xu, Z., Guo, C., Ye, Q., Shi, Y., Sun, Y., Zhang, J., Huang, J., Huang, Y., Zeng, C., Zhang, X. Z., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26697-8 · Cited by 100 · see citing works
KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition
Pan, Y., Han, H., Hu, H., Wang, H., Song, Y., Yuan, H., Tong, X., Patel, A. S., Misirlioğlu, S., Tang, S., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.11.015 · Cited by 100 · see citing works
Self-citationImproving outcomes in patients with oesophageal cancer
Shah, M. A., Altorki, N. K., Patel, P., Harrison, S. W., Bass, A. J., & Abrams, J. A. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00757-y · Cited by 101 · see citing works
Self-citationLu, H., Liu, C., Velazquez, R., Wang, H., Dunkl, L. M., Kazic-Legueux, M., Haberkorn, A., Billy, E., Manchado, E., Brachmann, S. M., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0852 · Cited by 90 · see citing works
Pharmacological Targeting of STK19 Inhibits Oncogenic NRAS-Driven Melanomagenesis
Yin, C., Zhu, B., Zhang, T., Liu, T., Chen, S., Liu, Y., Li, X., Miao, X., Li, S., Mi, X., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.002 · Cited by 92 · see citing works
Wang-Bishop, L., Chen, Z., Gomaa, A., Lockhart, A. C., Salaria, S. N., Wang, J.-L., Lewis, K. B., Ecsedy, J., Washington, K., Beauchamp, R., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.10.030 · Cited by 89 · see citing works
Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors
Bagdanoff, J. T., Chen, Z., Acker, M., Chen, Y., Chan, H., Dore, M., Firestone, B., Fodor, M., García‐Fortanet, J., Hentemann, M., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01725 · Cited by 91 · see citing works
Leung, C. O. N., Tong, M., Chung, K. P. S., Zhou, L., Che, N., Tang, K. H., Ding, J., Lau, E. Y.-T., Ng, I. O., Ma, S., et al. (2019) · Hepatology · doi:10.1002/hep.30989 · Cited by 88 · see citing works
Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS
Yin, G., Huang, J., Petela, J., Jiang, H., Zhang, Y., Gong, S., Wu, J., Liu, B., Shi, J., & Gao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01441-4 · Cited by 87 · see citing works
KRAS G12C Mutations in NSCLC: From Target to Resistance
Addeo, A., Banna, G. L., & Friedlaender, A. (2021) · Cancers · doi:10.3390/cancers13112541 · Cited by 84 · see citing works
SOS GEFs in health and disease
Baltanás, F. C., Zarich, N., Rojas-Cabañeros, J. M., & Santos, E. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188445 · Cited by 100 · see citing works
Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges
Tang, D., Kroemer, G., & Kang, R. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01422-7 · Cited by 80 · see citing works
Najafi, M., Ahmadi, A., & Mortezaee, K. (2019) · Cell Biology International · doi:10.1002/cbin.11187 · Cited by 78 · see citing works
Santana-Codina, N., Chandhoke, A. S., Yu, Q., Małachowska, B., Kuljanin, M., Gikandi, A., Stańczak, M., Gableske, S., Jedrychowski, M. P., Scott, D. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.021 · Cited by 77 · see citing works
Kim, J. W., Márquez, C. P., Kostyrko, K., Koehne, A. L., Marini, K. D., Simpson, D. R., Lee, A. G., Leung, S. G., Sayles, L. C., Shrager, J. B., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0612-2 · Cited by 76 · see citing works
Therapeutics Targeting Mutant KRAS
Thein, K. Z., Biter, A. B., & Hong, D. S. (2020) · Annual Review of Medicine · doi:10.1146/annurev-med-080819-033145 · Cited by 75 · see citing works
Catenacci, D. V. T., Moya, S. M., Lomnicki, S., Chase, L. M., Peterson, B. F., Reizine, N. M., Alpert, L., Setia, N., Xiao, S., Hart, J. A. L., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1408 · Cited by 72 · see citing works
Self-citationGenomics and Targeted Therapies in Gastroesophageal Adenocarcinoma
Nagaraja, A. K., Kikuchi, O., & Bass, A. J. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0487 · Cited by 70 · see citing works
Self-citationEarly stage gastric adenocarcinoma: clinical and molecular landscapes
Hirata, Y., Noorani, A., Song, S., Wang, L., & Ajani, J. A. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00767-w · Cited by 73 · see citing works
Sethi, N. S., Kikuchi, O., Duronio, G. N., Stachler, M. D., McFarland, J. M., Ferrer-Luna, R., Zhang, Y., Bao, C., Bronson, R. T., Patil, D. T., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0574-9 · Cited by 67 · see citing works
Self-citationThe role of MAPK pathway in gastric cancer: unveiling molecular crosstalk and therapeutic prospects
Yuan, W., Shi, Y., Dai, S., Deng, M., Zhu, K., Xu, Y., Chen, Z., Zhou, X., Zhang, T., & Song, L. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05998-8 · Cited by 68 · see citing works
Bala, P., Rennhack, J. P., Aitymbayev, D., Morris, C. X., Moyer, S. M., Duronio, G. N., Doan, K. T., Li, Z., Liang, X., Hornick, J. L., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf0927 · Cited by 67 · see citing works
Gao, J., Wu, Z., Zhao, M., Zhang, R., Li, M., Sun, D., Cheng, H., Qi, X., Shen, Y., Xu, Q., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.08.006 · Cited by 64 · see citing works
Self-citationProtein Tyrosine Phosphatases: Mechanisms in Cancer
Sivaganesh, V., Sivaganesh, V., Scanlon, C., Iskander, A., Maher, S., Le, T. H., & Peethambaran, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312865 · Cited by 64 · see citing works
Wang, K., Liu, Y., Li, J., Xiao, C., Wang, Y., Gu, W., Li, Y., Xia, Y., Yan, T., Yang, M.-H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33761-4 · Cited by 64 · see citing works
Rocca, A., Braga, L., Volpe, M. C., Maiocchi, S., & Generali, D. (2022) · Cancers · doi:10.3390/cancers14215306 · Cited by 65 · see citing works
Overcoming Resistance to Drugs Targeting KRAS Mutation
Jiao, D., & Yang, S. (2020) · The Innovation · doi:10.1016/j.xinn.2020.100035 · Cited by 61 · see citing works
Ren, Q., Zhang, P., Zhang, X., Feng, Y., Li, L., Lin, H., & Yu, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1199040 · Cited by 63 · see citing works
Valencia-Sama, I., Ladumor, Y., Kee, L., Adderley, T., Christopher, G., Robinson, C. M., Kano, Y., Ohh, M., & Irwin, M. S. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3822 · Cited by 62 · see citing works
Strategies to overcome drug resistance using SHP2 inhibitors
Liu, M., Gao, S., Elhassan, R. M., Hou, X., & Fang, H. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.037 · Cited by 59 · see citing works
SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling
Niogret, C., Birchmeier, W., & Guarda, G. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02468 · Cited by 48 · see citing works
Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Hao, H.-X., Wang, H., Liu, C., Kovats, S., Velazquez, R., Lu, H., Pant, B., Shirley, M., Meyer, M. J., Pu, M., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0170 · Cited by 53 · see citing works
Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance
Zandi, Z., Kashani, B., Alishahi, Z., Pourbagheri‐Sigaroodi, A., Esmaeili, F., Ghaffari, S. H., Bashash, D., & Momeny, M. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-021-03874-2 · Cited by 52 · see citing works
Imamura, Y., Watanabe, M., Oki, E., Morita, M., & Baba, H. (2020) · Annals of Gastroenterological Surgery · doi:10.1002/ags3.12406 · Cited by 52 · see citing works
Self-citationLong-read sequencing for non-small-cell lung cancer genomesPreprint
Sakamoto, Y., Xu, L., Seki, M., Yokoyama, T., Kasahara, M., Kashima, Y., Ohashi, A., Shimada, Y., Motoi, N., Tsuchihara, K., et al. (2020) · Genome Research · doi:10.1101/gr.261941.120 · Cited by 45 · see citing works
Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma
Atabay, E. K., Mecca, C., Wang, Q., Ambrogio, C., Mota, I. A., Prokoph, N., Mura, G., Martinengo, C., Patrucco, E., Leonardi, G. C., et al. (2021) · Blood · doi:10.1182/blood.2020008136 · Cited by 51 · see citing works
Chen, W. S., Liang, Y., Zong, M., Liu, J. J., Kaneko, K., Hanley, K. L., Zhang, K., & Feng, G.-S. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109974 · Cited by 50 · see citing works
Self-citationGebregiworgis, T., Kano, Y., St-Germain, J., Radulovich, N., Udaskin, M. L., Mentes, A., Huang, R., Poon, B. P. K., He, W., Valencia-Sama, I., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26526-y · Cited by 49 · see citing works
Avery, T. Y., Köhler, N., Zeiser, R., Brummer, T., & Ruess, D. A. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.931774 · Cited by 51 · see citing works
Structural impact of GTP binding on downstream KRAS signaling
Menyhárd, D. K., Pálfy, G., Orgován, Z., Vida, I., Keserű, G. M., & Perczel, A. (2020) · Chemical Science · doi:10.1039/d0sc03441j · Cited by 50 · see citing works
A KRAS-responsive long non-coding RNA controls microRNA processing
Shi, L., Magee, P., Fassan, M., Sahoo, S., Leong, H. S., Lee, D. C. H., Sellers, R., Brullé, L., Cairo, S., Monteverde, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22337-3 · Cited by 50 · see citing works
Targeting KRAS mutations in pancreatic cancer: opportunities for future strategies
Linehan, A., O’Reilly, M., McDermott, R., & O'Kane, G. M. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1369136 · Cited by 50 · see citing works
Thinking Differently about Cancer Treatment Regimens
Settleman, J., Neto, J. M. F., & Bernards, R. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1187 · Cited by 48 · see citing works
Liu, M., Gao, S., Tao, L., Qiu, X., Yang, X., Fang, H., & Hou, X. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00866 · Cited by 45 · see citing works
PTPN11 Plays Oncogenic Roles and Is a Therapeutic Target for BRAF Wild-Type Melanomas
Hill, K. S., Roberts, E. R., Wang, X., Marin, E. M., Park, T. D., Son, S., Ren, Y., Fang, B., Yoder, S., Kim, S., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-18-0777 · Cited by 46 · see citing works
From bench to bedside: current development and emerging trend of KRAS-targeted therapy
Chen, Y., Liu, Q.-P., Xie, H., & Ding, J. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01194-4 · Cited by 44 · see citing works
Resistance Mechanisms to SYK Inhibition in Acute Myeloid Leukemia
Cremer, A., Ellegast, J. M., Alexe, G., Frank, E. S., Ross, L. S., Chu, S. H., Pikman, Y., Robichaud, A. L., Goodale, A. B., Häupl, B., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0209 · Cited by 41 · see citing works
Frank, K. J., Mulero-Sánchez, A., Berninger, A., Ruiz-Cañas, L., Bosma, A., Görgülü, K., Wu, N., Diakopoulos, K. N., Kaya-Aksoy, E., Ruess, D. A., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100815 · Cited by 40 · see citing works
Possible Influences of Endogenous and Exogenous Ligands on the Evolution of Human Siglecs
Angata, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02885 · Cited by 40 · see citing works
An allosteric interaction controls the activation mechanism of SHP2 tyrosine phosphatase
Anselmi, M., & Hub, J. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-75409-7 · Cited by 39 · see citing works
Shipping out MEK inhibitor resistance with SHP2 inhibitors
Torres-Ayuso, P., & Brognard, J. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0915 · Cited by 37 · see citing works
Targeting farnesylation as a novel therapeutic approach in HRAS-mutant rhabdomyosarcoma
Odeniyide, P., Yohe, M. E., Pollard, K., Vaseva, A. V., Calizo, A., Zhang, L., Rodríguez, F. J., Gross, J. M., Allen, A. N., Wan, X., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02305-x · Cited by 38 · see citing works
Wang, S. C., Yeu, Y., Hammer, S. T. G., Xiao, S., Zhu, M., Hong, C., Clemenceau, J. R. V., Yoon, L. Y., Nassour, I., Shen, J., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2918 · Cited by 38 · see citing works
Blocking STAT3 signaling augments MEK/ERK inhibitor efficacy in esophageal squamous cell carcinoma
Zheng, Z.-Y., Chu, M.-Y., Lin, W., Zheng, Y.-Q., Xu, X., Chen, Y., Liao, L., Wu, Z., Wang, S., Li, E., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04941-3 · Cited by 38 · see citing works
Self-citationEssakly, A., Loeser, H., Kraemer, M., Alakus, H., Chon, S., Zander, T., Buettner, R., Hillmer, A. M., Bruns, C. J., Schroeder, W., et al. (2019) · Translational Oncology · doi:10.1016/j.tranon.2019.10.013 · Cited by 37 · see citing works
A New View of Activating Mutations in Cancer
Nussinov, R., Tsai, C., & Jang, H. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-2125 · Cited by 35 · see citing works
Targeting Mutant KRAS in Pancreatic Cancer: Futile or Promising?
Nollmann, F. I., & Ruess, D. A. (2020) · Biomedicines · doi:10.3390/biomedicines8080281 · Cited by 33 · see citing works
Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2–mediated signaling
Sang, Y., Hou, Y., Cheng, R., Zheng, L., Alvarez, A. A., Hu, B., Cheng, S., Zhang, W., Li, Y., & Feng, H. (2019) · Neuro-Oncology · doi:10.1093/neuonc/noz107 · Cited by 34 · see citing works
Dampening oncogenic RAS signaling
Bivona, T. G. (2019) · Science · doi:10.1126/science.aav6703 · Cited by 33 · see citing works
Tsujino, T., Sugito, N., Taniguchi, K., Honda, R. P., Komura, K., Yoshikawa, Y., Takai, T., Minami, K., Kuranaga, Y., Shinohara, H., et al. (2019) · Cancer Science · doi:10.1111/cas.14035 · Cited by 33 · see citing works
Mutant p53 induces a hypoxia transcriptional program in gastric and esophageal adenocarcinoma
Sethi, N. S., Kikuchi, O., McFarland, J. M., Zhang, Y., Chung, M., Kafker, N., Islam, M., Lampson, B. L., Chakraborty, A. A., Kaelin, W. G., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.128439 · Cited by 33 · see citing works
Self-citationTargeting KRAS in Colorectal Cancer: A Bench to Bedside Review
Bteich, F., Mohammadi, M., Li, T., Bhat, M. A., Sofianidi, A. A., Wei, N., & Kuang, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512030 · Cited by 32 · see citing works
Self-citationTyrosine phosphatase PTPN11/SHP2 in solid tumors - bull’s eye for targeted therapy?
Chen, X., Keller, S. J., Hafner, P., Alrawashdeh, A. Y., Avery, T. Y., Norona, J., Zhou, J., & Ruess, D. A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1340726 · Cited by 32 · see citing works
Self-citationGarcía‐Navas, R., Liceras-Boillos, P., Gómez, C., Baltanás, F. C., Calzada, N., Nuevo‐Tapioles, C., Cuezva, J. M., & Santos, E. (2021) · Oncogene · doi:10.1038/s41388-021-01886-3 · Cited by 32 · see citing works
SOS2 Comes to the Fore: Differential Functionalities in Physiology and Pathology
Baltanás, F. C., García‐Navas, R., & Santos, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126613 · Cited by 32 · see citing works
Yang, W., Zhang, M., Zhang, T.-X., Liu, J.-H., Hao, M.-W., Yan, X., Gao, H., Lei, Q.-Y., Cui, J., & Zhou, X. (2024) · JCI Insight · doi:10.1172/jci.insight.178535 · Cited by 31 · see citing works
Self-citation
- 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
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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 ›
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