SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

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The blockade of immune checkpoints in cancer immunotherapy

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Molecular mechanisms of T cell co-stimulation and co-inhibition

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CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms

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T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

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Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2

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Crystal Structure of the Tyrosine Phosphatase SHP-2

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Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

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LAG3 (CD223) as a Cancer Immunotherapy Target

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SH2-Containing Phosphotyrosine Phosphatase as a Target of Protein-Tyrosine Kinases

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Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth

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B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator

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Immune suppressive mechanisms in the tumor microenvironment

Munn, D. H., & Bronte, V. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.10.009 · Cited by 519 · see citing works

VISTA is an immune checkpoint molecule for human T cells

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Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase

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SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo

Mainardi, S., Mulero-Sánchez, A., Prahallad, A., Germano, G., Bosma, A., Krimpenfort, P., Lieftink, C., Steinberg, J. D., de Wit, N., Gonçalves-Ribeiro, S., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0023-9 · Cited by 320 · see citing works

Allosteric inhibition of SHP2: identification of a potent, selective, and orally efficacious phosphatase inhibitor

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Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition

Wong, G. S., Zhou, J., Liu, J. B., Wu, Z., Xu, X., Li, T., Xu, D., Schumacher, S. E., Puschhof, J., McFarland, J., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0022-x · Cited by 266 · see citing works

Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop

Aceto, N., Sausgruber, N., Brinkhaus, H., Gaidatzis, D., Martiny‐Baron, G., Mazzarol, G., Confalonieri, S., Quarto, M., Hu, G., Balwierz, P. J., et al. (2012) · Nature Medicine · doi:10.1038/nm.2645 · Cited by 263 · see citing works

PD-1/SHP-2 Inhibits Tc1/Th1 Phenotypic Responses and the Activation of T Cells in the Tumor Microenvironment

Li, J., Jie, H.-B., Lei, Y. L., Gildener‐Leapman, N., Trivedi, S., Green, T., Kane, L., & Ferris, R. L. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1215 · Cited by 252 · see citing works

Protein tyrosine phosphatase SHP-2: A proto-oncogene product that promotes Ras activation

Matozaki, T., Murata, Y., Saito, Y., Okazawa, H., & Ohnishi, H. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01257.x · Cited by 240 · see citing works

SHP2 sails from physiology to pathology

Tajan, M., de Rocca Serra, A., Valet, P., Edouard, T., & Yart, A. (2015) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2015.08.005 · Cited by 232 · see citing works

The Programmed Death-1 Immune-Suppressive Pathway: Barrier to Antitumor Immunity

Ostrand‐Rosenberg, S., Horn, L. A., & Haile, S. T. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401572 · Cited by 228 · see citing works

The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functions

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Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo

Rota, G., Niogret, C., Dang, A. T., Barros, C. R., Fonta, N. P., Alfei, F., Morgado, L., Zehn, D., Birchmeier, W., Vivier, E., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.026 · Cited by 155 · see citing works

PTPN11/Shp2 overexpression enhances liver cancer progression and predicts poor prognosis of patients

Han, T., Xiang, D., Sun, W. C., Liu, N., Sun, H., Wen, W., Shen, W.-F., Wang, R., Chen, C. Y., Wang, X. B., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.03.036 · Cited by 141 · see citing works

Overexpression of Shp2 tyrosine phosphatase is implicated in leukemogenesis in adult human leukemia

Xu, R., Yu, Y., Zheng, S. S., Zhao, X., Dong, Q., He, Z., Liang, Y., Lu, Q., Fang, Y., Gan, X., et al. (2005) · Blood · doi:10.1182/blood-2004-10-4057 · Cited by 121 · see citing works

Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

Peng, S., Hang, N., Liu, W., Guo, W., Jiang, C., Yang, X., Xu, Q., & Sun, Y. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.02.002 · Cited by 113 · see citing works

SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans

Liu, K.-W., Feng, H., Bachoo, R. M., Kazlauskas, A., Smith, E. M., Symes, K., Hamilton, R. L., Nagane, M., Nishikawa, R., Hu, B., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43690 · Cited by 92 · see citing works

T Cell Ig and Mucin Domain Proteins and Immunity

Kane, L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902937 · Cited by 75 · see citing works

SHP2 forecast for the immune system: fog gradually clearing.

Salmond, R. J., & Alexander, D. (2006) · Trends in immunology · doi:10.1016/j.it.2006.01.007 · Cited by 69 · see citing works

Shp2 deletion in hepatocytes suppresses hepatocarcinogenesis driven by oncogenic β-Catenin, PIK3CA and MET

Liu, J. J., Li, Y., Chen, W. S., Liang, Y., Wang, G., Zong, M., Kaneko, K., Xu, R., Karin, M., & Feng, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.02.014 · Cited by 64 · see citing works

Selective Sequestration of STAT1 in the Cytoplasm via Phosphorylated SHP-2 Ameliorates Murine Experimental Colitis

Wu, X., Guo, W., Wu, L., Gu, Y., Gu, L., Xu, S.-H., Wu, X., Shen, Y., Ke, Y., Tan, R. X., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201006 · Cited by 56 · see citing works

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

Sang, X., Wang, R., Han, Y., Zhang, C., Shen, H., Yang, Z., Xiong, Y., Liu, H., Liu, S., Li, R., et al. (2017) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2017.02.005 · Cited by 37 · see citing works

T lymphocyte SHP2-deficiency triggers anti-tumor immunity to inhibit colitis-associated cancer in mice

Liu, W., Guo, W., Shen, L., Chen, Z., Luo, Q., Luo, X., Feng, G., Shu, Y., Gu, Y., Xu, Q., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13812 · Cited by 35 · see citing works

Ptpn11 Deletion in CD4+ Cells Does Not Affect T Cell Development and Functions but Causes Cartilage Tumors in a T Cell-Independent Manner

Miah, S. M. S., Jayasuriya, C. T., Salter, A. I., Reilly, E. C., Fugère, C., Yang, W., Chen, Q., & Brossay, L. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01326 · Cited by 18 · see citing works

T cell activation is reduced by the catalytically inactive form of protein tyrosine phosphatase SHP-2.

Dong, B., Gao, Y., Zheng, X., Gao, G., Gu, H., Chen, X., & Zhang, J. (2015) · PubMed Central · Cited by 7 · see citing works

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works

JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression

Owen, K. L., Brockwell, N. K., & Parker, B. S. (2019) · Cancers · doi:10.3390/cancers11122002 · Cited by 711 · 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

The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy

Yang, Q., Guo, N., Zhou, Y., Chen, J., Wei, Q., & Han, M. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.04.004 · Cited by 471 · see citing works

Molecular mechanism of SHP2 activation by PD-1 stimulation

Marasco, M., Berteotti, A., Weyershaeuser, J., Thorausch, N., Sikorska, J., Krausze, J., Brandt, H., Kirkpatrick, J., Ríos, P., Schamel, W. W. A., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay4458 · Cited by 268 · see citing works

Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC

Chen, S., Zhu, S., Pei, X., Qiu, B., Xiong, D., Long, X., Lin, K., Lü, F., Xu, J., & Wu, Y. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01448-x · Cited by 259 · 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

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

Targeting SHP2 as a promising strategy for cancer immunotherapy

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

Drugging KRAS: Current perspectives and state-of-art review

Parikh, K., Banna, G., Liu, S. V., Friedlaender, A., Desai, A., Subbiah, V., & Addeo, A. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01375-4 · Cited by 164 · see citing works

Insulin receptor endocytosis in the pathophysiology of insulin resistance

Hall, C., Yu, H., & Choi, E. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0456-3 · Cited by 137 · see citing works

Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies

Song, Z., Wang, M., Yang, G., Chen, X.-P., Xu, Z., Sun, Y., & Xiong, X. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.07.010 · Cited by 137 · see citing works

Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing

Wang, Z., Kang, W.-T., Li, O., Qi, F., Wang, J., You, Y., He, P., Suo, Z., Zheng, Y., & Liu, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.005 · Cited by 139 · see citing works

Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders

Stanford, S. M., & Bottini, N. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00618-w · Cited by 136 · see citing works

Allosteric SHP2 inhibitors in cancer: Targeting the intersection of RAS, resistance, and the immune microenvironment

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

Double-edged roles of protein tyrosine phosphatase SHP2 in cancer and its inhibitors in clinical trials

Song, Y., Zhao, M., Zhang, H., & Yu, B. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107966 · Cited by 125 · 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

Turn and Face the Strange: A New View on Phosphatases

Köhn, M. (2020) · ACS Central Science · doi:10.1021/acscentsci.9b00909 · Cited by 113 · see citing works

SHP-2 and PD-L1 Inhibition Combined with Radiotherapy Enhances Systemic Antitumor Effects in an Anti–PD-1–Resistant Model of Non–Small Cell Lung Cancer

Chen, D., Barsoumian, H. B., Yang, L., Younes, A. I., Verma, V., Hu, Y., Menon, H., Wasley, M., Masropour, F., Mosaffa, S., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0744 · Cited by 107 · see citing works

Druggable cancer phosphatases

Vainonen, J. P., Momeny, M., & Westermarck, J. K. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe2967 · Cited by 105 · see citing works

SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment

Sodir, N. M., Pathria, G., Adamkewicz, J. I., Kelley, E. H., Sudhamsu, J., Merchant, M. A., Chiarle, R., & Maddalo, D. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0383 · Cited by 103 · see citing works

KRAS G12C–Mutant Non–Small Cell Lung Cancer

Veluswamy, R., Mack, P. C., Houldsworth, J., Elkhouly, E., & Hirsch, F. R. (2021) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.02.002 · Cited by 96 · see citing works

Allosteric Inhibition of SHP2 Stimulates Antitumor Immunity by Transforming the Immunosuppressive Environment

Quintana, E., Schulze, C. J., Myers, D. R., Choy, T. J., Mordec, K., Wildes, D. P., Shifrin, N. T., Belwafa, A., Koltun, E. S., Gill, A. L., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3038 · Cited by 98 · see citing works

Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity

Deng, H., Tan, S., Gao, X., Zou, C., Xu, C., Tu, K., Song, Q., Fan, F., Huang, W., & Zhang, Z. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.07.004 · Cited by 95 · see citing works

A novel cyclic peptide targeting LAG-3 for cancer immunotherapy by activating antigen-specific CD8+ T cell responses

Zhai, W., Zhou, X., Wang, H., Li, W., Chen, G., Sui, X., Li, G., Qi, Y., & Gao, Y. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.005 · Cited by 93 · see citing works

Mechanism of allosteric activation of SIRT6 revealed by the action of rationally designed activators

Lu, S., Chen, Y.-Y., Wei, J., Zhao, M., Ni, D., He, X., & Zhang, J. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.09.010 · Cited by 93 · see citing works

Inhibition of NLRP3 inflammasome-mediated pyroptosis in macrophage by cycloastragenol contributes to amelioration of imiquimod-induced psoriasis-like skin inflammation in mice

Deng, G., Chen, W., Wang, P., Zhan, T., Zheng, W., Gu, Z., Wang, X., Ji, X., & Sun, Y. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105682 · Cited by 92 · see citing works

Detachable Liposomes Combined Immunochemotherapy for Enhanced Triple-Negative Breast Cancer Treatment through Reprogramming of Tumor-Associated Macrophages

Chen, M., Miao, Y., Qian, K., Zhou, X. H., Guo, L., Qiu, Y., Wang, R., Gan, Y., & Zhang, X. (2021) · Nano Letters · doi:10.1021/acs.nanolett.1c01210 · Cited by 86 · see citing works

Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling

Sun, Z., Liu, Q., Lv, Z., Li, J., Xu, X., Sun, H., Wang, M., Sun, K., Shi, T., Liu, Z., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.010 · Cited by 85 · see citing works

Mechanisms of Immunosuppression in Colorectal Cancer

Zhang, Y., Rajput, A., Jin, N. Y., & Wang, J. (2020) · Cancers · doi:10.3390/cancers12123850 · Cited by 81 · see citing works

Molecular correlates and therapeutic targets in T cell-inflamed versus non-T cell-inflamed tumors across cancer types

Bao, R., Stapor, D. C., & Luke, J. J. (2020) · Genome Medicine · doi:10.1186/s13073-020-00787-6 · Cited by 78 · see citing works

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms

Wang, Y., Mohseni, M., Grauel, A., Diez, J. E., Guan, W., Liang, S., Choi, J. E., Pu, M., Chen, D., Laszewski, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-80999-x · Cited by 73 · see citing works

DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

Wang, Y., Wei, B., Wang, D., Wu, J., Gao, J., Zhong, H., Sun, Y., Xu, Q., Liu, W., Gu, Y., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.043 · Cited by 73 · see citing works

Accessory proteins of the RAS-MAPK pathway: moving from the side line to the front line

Pudewell, S., Wittich, C., Jasemi, N. S. K., Bazgir, F., & Ahmadian, M. R. (2021) · Communications Biology · doi:10.1038/s42003-021-02149-3 · Cited by 72 · see citing works

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Ni, D., Chai, Z., Wang, Y., Li, M., Yu, Z., Liu, Y., Lu, S., & Zhang, J. (2021) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1585 · Cited by 67 · see citing works

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

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

SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

Chen, H., Libring, S., Ruddraraju, K. V., Miao, J., Solorio, L., Zhang, Z., & Wendt, M. K. (2020) · Oncogene · doi:10.1038/s41388-020-01488-5 · Cited by 64 · see citing works

Allosteric binding sites at the receptor–lipid bilayer interface: novel targets for GPCR drug discovery

Wang, Y., Yu, Z., Xiao, W., Lu, S., & Zhang, J. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.12.001 · Cited by 63 · see citing works

Macrophage-mediated tumor-targeted delivery of engineered Salmonella typhimurium VNP20009 in anti-PD1 therapy against melanoma

Wu, L., Li, L., Li, S., Liu, L., Xin, W., Li, C., Yin, X., Xu, X., Bao, F., & Hua, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.05.006 · Cited by 63 · see citing works

Adverse Effects of Anti-PD-1/PD-L1 Therapy in Non-small Cell Lung Cancer

Su, C., Wang, H., Liu, Y., Guo, Q., Zhang, L., Li, J., Zhou, W., Yan, Y., Zhou, X., & Zhang, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.554313 · Cited by 63 · 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

Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer

Wei, J., Long, Y., Guo, R., Liu, X., Tang, X., Rao, J., Yin, S., Zhang, Z., Li, M., & He, Q. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.01.018 · Cited by 55 · see citing works

Targeting metabolism to reverse T‐cell exhaustion in chronic viral infections

Sears, J. D., Waldron, K. J., Wei, J. N., & Chang, C. (2020) · Immunology · doi:10.1111/imm.13238 · Cited by 49 · see citing works

Role of natural products in tumor therapy from basic research and clinical perspectives

Wang, Z., Liu, Z., Qu, J., Sun, Y., & Zhou, W. (2024) · Acta Materia Medica · doi:10.15212/amm-2023-0050 · Cited by 48 · see citing works

Medicinal chemistry strategies for the development of protein tyrosine phosphatase SHP2 inhibitors and PROTAC degraders

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Discovery of Novel Src Homology-2 Domain-Containing Phosphatase 2 and Histone Deacetylase Dual Inhibitors with Potent Antitumor Efficacy and Enhanced Antitumor Immunity

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

Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy

Castro-Sanchez, P., Teagle, A. R., Prade, S., & Zamoyska, R. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.608747 · Cited by 44 · see citing works

Targeted Degradation of the Oncogenic Phosphatase SHP2

Vemulapalli, V., Donovan, K. A., Seegar, T. C. M., Rogers, J. M., Bae, M., Lumpkin, R. J., Cao, R., Henke, M. T., Ray, S. S., Fischer, E. S., et al. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00377 · Cited by 43 · see citing works

Extensive preclinical validation of combined RMC-4550 and LY3214996 supports clinical investigation for KRAS mutant pancreatic cancer

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Building on the backbone of CD47-based therapy in cancer: Combination strategies, mechanisms, and future perspectives

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Allosterically activating SHP2 by oleanolic acid inhibits STAT3–Th17 axis for ameliorating colitis

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Synergistic antitumor activity of artesunate and HDAC inhibitors through elevating heme synthesis via synergistic upregulation of ALAS1 expression

Chen, C., Chen, K., Feng, Z., Wen, X., & Sun, H. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.05.001 · Cited by 40 · see citing works

If small molecules immunotherapy comes, can the prime be far behind?

Zhang, J., Zhang, Y., Qu, B., Yang, H., Hu, S., & Dong, X. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113356 · Cited by 40 · see citing works

CXCR6-based immunotherapy in autoimmune, cancer and inflammatory infliction

Li, T., Pan, J., Chen, H., Fang, Y., & Sun, Y. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.03.012 · Cited by 39 · see citing works

Reversing T Cell Dysfunction to Boost Glioblastoma Immunotherapy by Paroxetine‐Mediated GRK2 Inhibition and Blockade of Multiple Checkpoints through Biomimetic Nanoparticles

Wang, T., Zhang, H., Han, Y., Zheng, Q. Y., Liu, H., Han, M., & Li, Z. (2023) · Advanced Science · doi:10.1002/advs.202204961 · Cited by 39 · see citing works

Inhibition of SHP-1 Expands the Repertoire of Antitumor T Cells Available to Respond to Immune Checkpoint Blockade

Snook, J. P., Soedel, A. J., Ekiz, H. A., O’Connell, R. M., & Williams, M. A. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0690 · Cited by 39 · see citing works

PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma

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Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity

Sitaram, P., Uyemura, B. S., Malarkannan, S., & Riese, M. J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235821 · Cited by 38 · see citing works

SH2 Domain–Containing Phosphatase 2 Inhibition Attenuates Osteoarthritis by Maintaining Homeostasis of Cartilage Metabolism via the Docking Protein 1/Uridine Phosphorylase 1/Uridine Cascade

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Targeting RAS mutants in malignancies: successes, failures, and reasons for hope

Yang, H. S., Zhou, X., Fu, D., Le, C., Wang, J., Zhou, Q., Liu, X., Yuan, Y., Ding, K., & Xiao, Q. (2022) · 癌症：英文版 · doi:10.1002/cac2.12377 · Cited by 35 · see citing works

Small molecule inhibitors for cancer immunotherapy and associated biomarkers – the current status

Schlicher, L., Green, L. G., Romagnani, A., & Renner, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1297175 · Cited by 34 · see citing works

A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors

Song, Y., Zhao, M., Wu, Y., Yu, B., & Liu, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.10.021 · Cited by 34 · see citing works

The role of KIR positive NK cells in diseases and its importance in clinical intervention

Asl, K. D., Velaei, K., Rafat, A., Nasrabadi, H. T., Movassaghpour, A. A., Mahdavi, M., & Charoudeh, H. N. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107361 · Cited by 34 · see citing works

Anti‐tumour potential of PD‐L1 / PD ‐1 post‐translational modifications

Zhou, S., Zhu, J., Xu, J., Gu, B., Zhao, Q., Luo, C., Gao, Z., Chin, Y. E., & Cheng, X. (2022) · Immunology · doi:10.1111/imm.13573 · Cited by 34 · see citing works

Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy

Tang, X., Qi, C., Zhou, H., & Liu, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.972906 · Cited by 33 · see citing works

Combination Approaches to Target PD-1 Signaling in Cancer

Moore, E. K., Strazza, M., & Mor, A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.927265 · Cited by 32 · see citing works

Natural killer cells as a double-edged sword in cancer immunotherapy: A comprehensive review from cytokine therapy to adoptive cell immunotherapy

Wu, Y., Li, J., Kaboli, P. J., Shen, J., Wu, X., Zhao, Y., Ji, H., Du, F., Zhou, Y., Wang, Y., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104691 · Cited by 32 · see citing works

Small-Molecule PROTACs for Cancer Immunotherapy

Liu, Z., Zhang, Y., Xiang, Y., & Kang, X. (2022) · Molecules · doi:10.3390/molecules27175439 · Cited by 29 · see citing works

Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches

Tojjari, A., Saeed, A., Sadeghipour, A., Kurzrock, R., & Cavalcante, L. L. (2023) · Cancers · doi:10.3390/cancers15225384 · Cited by 30 · see citing works

Biology, pathology, and therapeutic targeting of RAS

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Spirodalesol analog 8A inhibits NLRP3 inflammasome activation and attenuates inflammatory disease by directly targeting adaptor protein ASC

Liu, W., Yang, J., Fang, S., Jiao, C., Gao, J., Zhang, A., Wu, T., Tan, R. X., Xu, Q., & Guo, W. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102696 · Cited by 28 · see citing works

Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma

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Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

Liu, W., Yin, Y., Wang, M., Fan, T., Zhu, Y., Shen, L., Peng, S., Gao, J., Deng, G., Meng, X., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011840 · Cited by 27 · see citing works

Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment

Ma, C., Kang, D., Gao, P., Zhang, W., Wu, X.-P., Xu, Z., Han, H., Zhang, L., Cai, Y., Wang, Y., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00360 · Cited by 25 · see citing works

Allosteric Inhibitors of SHP2: An Updated Patent Review (2015-2020)

Wu, J., Zhang, H., Zhao, G., & Wang, R. (2020) · Current Medicinal Chemistry · doi:10.2174/1568011817666200928114851 · Cited by 24 · see citing works

Advances in SHP2 tunnel allosteric inhibitors and bifunctional molecules

Guo, Z., Duan, Y., Sun, K., Zheng, T., Liu, J., Xu, S., & Xu, J. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116579 · Cited by 25 · see citing works

SHP2 Targets ITK Downstream of PD-1 to Inhibit T Cell Function

Strazza, M., Adam, K. R., Lerrer, S., Straube, J., Sandigursky, S., Ueberheide, B. M., & Mor, A. (2021) · Inflammation · doi:10.1007/s10753-021-01437-8 · Cited by 23 · see citing works

Activating Mutation of SHP2 Establishes a Tumorigenic Phonotype Through Cell-Autonomous and Non-Cell-Autonomous Mechanisms

Dong, L., Han, D. W., Meng, X., Xu, M., Zheng, C., & Qin, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.630712 · Cited by 23 · see citing works

The K-Ras(G12D)-inhibitory peptide KS-58 suppresses growth of murine CT26 colorectal cancer cell-derived tumors

Sakamoto, K., Lin, B., Nunomura, K., Izawa, T., & Nakagawa, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-12401-3 · Cited by 21 · see citing works

Loss of hnRNP A1 in murine skeletal muscle exacerbates high-fat diet-induced onset of insulin resistance and hepatic steatosis

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SHP2 allosteric inhibitor TK-453 alleviates psoriasis-like skin inflammation in mice via inhibition of IL-23/Th17 axis

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Emerging chemical scaffolds with potential SHP2 phosphatase inhibitory capabilities – A comprehensive review

Tripathi, R. K. P., & Ayyannan, S. R. (2020) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13807 · Cited by 18 · see citing works

Therapeutic Suppression of FAK-AKT Signaling Overcomes Resistance to SHP2 Inhibition in Colorectal Carcinoma

Li, Y., Yuan, Y., Zhang, F., Guo, A., Cao, F., Song, M., Fu, Y., Xu, X., Shen, H., Zheng, S., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.739501 · Cited by 18 · see citing works

Current studies and future promises of PD-1 signal inhibitors in cervical cancer therapy

Awadasseid, A., Zhou, Y., Zhang, K., Tian, K., Wu, Y., & Zhang, W. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114057 · Cited by 18 · see citing works

Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance

Zhao, Y., & Jiang, L. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2024.10.008 · Cited by 17 · see citing works

Discovery of a potent and selective allosteric inhibitor targeting the SHP2 tunnel site for RTK-driven cancer treatment

Luo, R., Fu, W., Shao, J., Ma, L., Shuai, S., Xu, Y. J., Jiang, Z., Ye, Z., Zheng, L., Zheng, L., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115305 · Cited by 17 · see citing works

Deubiquitinase USP24 activated by IL-6/STAT3 enhances PD-1 protein stability and suppresses T cell antitumor response

Hsieh, H.-C., Young, M.-J., Chen, K., Su, W., Lin, C., Yen, Y., Hung, J., & Wang, Y. (2025) · Science Advances · doi:10.1126/sciadv.adt4258 · Cited by 16 · see citing works

SHP2 as a Potential Therapeutic Target in Diffuse-Type Gastric Carcinoma Addicted to Receptor Tyrosine Kinase Signaling

Nagamura, Y., Miyazaki, M., Nagano, Y., Tomiyama, A., Ohki, R., Yanagihara, K., Sakai, R., & Yamaguchi, H. (2021) · Cancers · doi:10.3390/cancers13174309 · Cited by 16 · see citing works

Small-molecule Modulators Targeting SHP2 for Cancer Therapy

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Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems

Zhang, H., Yang, X., Huang, Y., Li, Y., Hu, Q., Wei, Q., Xu, W., Ding, W., Guo, Y., & Shen, J. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c00579 · Cited by 16 · see citing works

A pan-cancer analysis confirms PTPN11’s potential as a prognostic and immunological biomarker

Cao, Y., Duan, H., Su, A., Xu, L., & Lai, B. (2022) · Aging · doi:10.18632/aging.204171 · Cited by 15 · see citing works

SHP-2-induced M2 polarization of tumor associated macrophages via IL-4 regulate colorectal cancer progression

Li, Z., Xi, J., Li, B., Liu, Y., Wang, G., Yu, B., Ma, H., Li, Z., & Zhang, Z. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1027575 · Cited by 15 · see citing works

Identification of linderalactone as a natural inhibitor of SHP2 to ameliorate CCl4-induced liver fibrosis

Zhang, Y., Cai, B., Li, Y., Xu, Y. J., Wang, Y., Zheng, L., Zheng, X., Yin, L., Chen, G., Wang, Y., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1098463 · Cited by 15 · see citing works

MicroRNA-217 modulates inflammation, oxidative stress, and lung injury in septic mice via SIRT1

Yan, J., Yang, F., Wang, D., Lü, Y., Liu, L., & Wang, Z. (2020) · Free Radical Research · doi:10.1080/10715762.2020.1852234 · Cited by 15 · see citing works

Methionine enkephalin inhibits colorectal cancer by remodeling the immune status of the tumor microenvironment

Wang, X., Li, S., Yan, S., Shan, Y., Wang, X., Jingbo, Z., Wang, Y., Shan, F., Griffin, N., & Sun, X. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109125 · Cited by 14 · see citing works

Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling

Zeke, A., Takács, T., Sok, P., Németh, K., Kirsch, K., Egri, P., Póti, Á., Bento, I., Tusnády, G., & Reményi, A. (2022) · Nature Communications · doi:10.1038/s41467-022-32918-5 · Cited by 14 · see citing works

From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond

Zhou, Y., Yao, Z., Lin, Y., & Zhang, H. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16070888 · Cited by 15 · see citing works

Design, Synthesis and Antitumor Activity of a Novel Class of SHP2 Allosteric Inhibitors with a Furanyl Amide-Based Scaffold

Zhu, C., Zhao, H., Yang, W., Chen, K., Liu, X., Yu, Y., Li, R., Tan, R., & Yu, Z. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01217 · Cited by 14 · see citing works

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms

Wang, Y., Mohseni, M., Grauel, A., Diez, J. E., Guan, W., Liang, S., Choi, J. E., Pu, M., Chen, D., Laszewski, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-80999-x · Cited by 73 · see citing works

Targeting SHP2 as a promising strategy for cancer immunotherapy

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

Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches

Tojjari, A., Saeed, A., Sadeghipour, A., Kurzrock, R., & Cavalcante, L. L. (2023) · Cancers · doi:10.3390/cancers15225384 · Cited by 30 · see citing works

Abstract A103: Allosteric inhibition of SHP2 induces antitumor immunity in PD-1-sensitive tumors through modulation of both innate and adaptive mechanisms

Quintana, E., Mordec, K., Nichols, R. J., Wildes, D. P., Schulze, C. J., Myers, D. R., Singh, M., Koltun, E. S., Gill, A. L., Kelsey, S. M., et al. (2019) · Cancer Immunology Research · doi:10.1158/2326-6074.cricimteatiaacr18-a103 · Cited by 1 · see citing works

OA12.03 Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC

Li, S., Tang, K. H., Khodadadi‐Jamayran, A., Jen, J., Han, H., Guidry, K., Chen, T., Hao, Y., Fedele, C., Zebala, J. A., et al. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.08.074