Skip to main content

Main menu

  • Home
  • About
    • About CBM
    • Editorial Board
    • Announcement
  • Articles
    • Ahead of print
    • Current Issue
    • Archive
    • Collections
    • Cover Story
  • For Authors
    • Instructions for Authors
    • Resources
    • Submit a Manuscript
  • For Reviewers
    • Become a Reviewer
    • Instructions for Reviewers
    • Resources
    • Outstanding Reviewer
  • Subscription
  • Alerts
    • Email Alerts
    • RSS Feeds
    • Table of Contents
  • Contact us
  • Other Publications
    • cbm

User menu

  • My alerts

Search

  • Advanced search
Cancer Biology & Medicine
  • Other Publications
    • cbm
  • My alerts
Cancer Biology & Medicine

Advanced Search

 

  • Home
  • About
    • About CBM
    • Editorial Board
    • Announcement
  • Articles
    • Ahead of print
    • Current Issue
    • Archive
    • Collections
    • Cover Story
  • For Authors
    • Instructions for Authors
    • Resources
    • Submit a Manuscript
  • For Reviewers
    • Become a Reviewer
    • Instructions for Reviewers
    • Resources
    • Outstanding Reviewer
  • Subscription
  • Alerts
    • Email Alerts
    • RSS Feeds
    • Table of Contents
  • Contact us
  • Follow cbm on Twitter
  • Visit cbm on Facebook
Research ArticleOriginal Article
Open Access

Apatinib enhances targeted immunotherapy via the IL-6-gp130-PI3K pathway in HER2-positive gastric cancer

Ruoxi Tian, Ziyue Sha, Shasha Zhang, Miao Gong, Jianhua Wu, Juntao Lu, Wei Guo, Zhaoxu Zheng and Zhanjun Guo
Cancer Biology & Medicine July 2026, 20250687; DOI: https://doi.org/10.20892/j.issn.2095-3941.2025.0687
Ruoxi Tian
1Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ziyue Sha
2Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shasha Zhang
2Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miao Gong
3Department of Histology and Embryology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianhua Wu
4Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juntao Lu
5Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Guo
5Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhaoxu Zheng
1Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zhaoxu Zheng
  • For correspondence: zzx_20003{at}126.com zjguo5886{at}hebmu.edu.cn
Zhanjun Guo
2Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zhanjun Guo
  • For correspondence: zzx_20003{at}126.com zjguo5886{at}hebmu.edu.cn
  • Article
  • Figures & Data
  • Info & Metrics
  • References
  • PDF
Loading

References

  1. 1.↵
    1. Sung H,
    2. Ferlay J,
    3. Siegel RL,
    4. Laversanne M,
    5. Soerjomataram I,
    6. Jemal A, et al.
    Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71: 209–49.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Selim JH,
    2. Shaheen S,
    3. Sheu WC,
    4. Hsueh CT.
    Targeted and novel therapy in advanced gastric cancer. Exp Hematol Oncol. 2019; 8: 25.
    OpenUrlPubMed
  3. 3.↵
    1. Ross JS,
    2. Slodkowska EA,
    3. Symmans WF,
    4. Pusztai L,
    5. Ravdin PM,
    6. Hortobagyi GN.
    The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009; 14: 320–68.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Mirza MB,
    2. Choi J,
    3. Marincola Smith P,
    4. Baechle JJ,
    5. Padmanabhan C,
    6. Holowatyj AN, et al.
    ERBB2 amplification in gastric cancer: a genomic insight into ethnic disparities. J Natl Cancer Inst. 2024; 116: 1830–3.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Li W,
    2. Zhang X,
    3. Du Y,
    4. Zhang Y,
    5. Lu J,
    6. Hu W, et al.
    HER2-targeted advanced metastatic gastric/gastroesophageal junction adenocarcinoma: treatment landscape and future perspectives. Biomark Res. 2022; 10: 71.
    OpenUrlPubMed
  6. 6.↵
    1. Bang YJ,
    2. Van Cutsem E,
    3. Feyereislova A,
    4. Chung HC,
    5. Shen L,
    6. Sawaki A, et al.
    Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376: 687–97.
    OpenUrlCrossRefPubMedWeb of Science
  7. 7.↵
    1. Pardoll DM.
    The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12: 252–64.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Sharma P,
    2. Allison JP.
    The future of immune checkpoint therapy. Science. 2015; 348: 56–61.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Okkenhaug K,
    2. Graupera M,
    3. Vanhaesebroeck B.
    Targeting PI3K in cancer: impact on tumor cells, their protective stroma, angiogenesis, and immunotherapy. Cancer Discov. 2016; 6: 1090–105.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Janjigian YY,
    2. Ajani JA,
    3. Moehler M,
    4. Shen L,
    5. Garrido M,
    6. Gallardo C, et al.
    First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol. 2024; 42: 2012–20.
    OpenUrlPubMed
  11. 11.↵
    1. Janjigian YY,
    2. Kawazoe A,
    3. Bai Y,
    4. Xu J,
    5. Lonardi S,
    6. Metges JP, et al.
    Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023; 402: 2197–208.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Ter Veer E,
    2. van den Ende T,
    3. Creemers A,
    4. de Waal L,
    5. van Oijen MGH,
    6. van Laarhoven HWM.
    Continuation of trastuzumab beyond progression in HER2-positive advanced esophagogastric cancer: a meta-analysis. Acta Oncol. 2018; 57: 1599–604.
    OpenUrlPubMed
  13. 13.↵
    1. Choi Y,
    2. Ko YS,
    3. Park J,
    4. Choi Y,
    5. Kim Y,
    6. Pyo JS, et al.
    HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer. World J Gastroenterol. 2016; 22: 9141–53.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Zito CR,
    2. Jilaveanu LB,
    3. Anagnostou V,
    4. Rimm D,
    5. Bepler G,
    6. Maira SM, et al.
    Multi-level targeting of the phosphatidylinositol-3-kinase pathway in non-small cell lung cancer cells. PLoS One. 2012; 7: e31331.
  15. 15.↵
    1. Pavlakis K,
    2. Bobos M,
    3. Batistatou A,
    4. Kotoula V,
    5. Eleftheraki AG,
    6. Stofas A, et al.
    P85 protein expression is associated with poor survival in HER2-positive patients with advanced breast cancer treated with trastuzumab. Pathol Oncol Res. 2015; 21: 273–82.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Folgiero V,
    2. Di Carlo SE,
    3. Bon G,
    4. Spugnini EP,
    5. Di Benedetto A,
    6. Germoni S, et al.
    Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast cancer cells. Cell Death Dis. 2012; 3: e440.
  17. 17.↵
    1. Lesniak D,
    2. Xu Y,
    3. Deschenes J,
    4. Lai R,
    5. Thoms J,
    6. Murray D, et al.
    β1-integrin circumvents the antiproliferative effects of trastuzumab in human epidermal growth factor receptor-2–positive breast cancer. Cancer Res. 2009; 69: 8620–8.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Alessi DR,
    2. Andjelkovic M,
    3. Caudwell B,
    4. Cron P,
    5. Morrice N,
    6. Cohen P, et al.
    Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 1996; 15: 6541–51.
    OpenUrlCrossRefPubMedWeb of Science
  19. 19.↵
    1. Doheny D,
    2. Sirkisoon S,
    3. Carpenter RL,
    4. Aguayo NR,
    5. Regua AT,
    6. Anguelov M, et al.
    Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis. Oncogene. 2020; 39: 6589–605.
    OpenUrlPubMed
  20. 20.↵
    1. de Oliveira Taveira M,
    2. Nabavi S,
    3. Wang Y,
    4. Tonellato P,
    5. Esteva FJ,
    6. Cantley LC, et al.
    Genomic characteristics of trastuzumab-resistant HER2-positive metastatic breast cancer. J Cancer Res Clin Oncol. 2017; 143: 1255–62.
    OpenUrlPubMed
  21. 21.↵
    1. Reddavid R,
    2. Dagatti S,
    3. Franco C,
    4. Puca L,
    5. Tomatis M,
    6. Corso S, et al.
    Molecularly targeted therapies for gastric cancer. State of the art. Cancers (Basel). 2021; 13: 4094.
    OpenUrlPubMed
  22. 22.↵
    1. Kim ST,
    2. Sa JK,
    3. Oh SY,
    4. Kim K,
    5. Hong JY,
    6. Kang WK, et al.
    Comprehensive molecular characterization of gastric cancer patients from phase II second-line ramucirumab plus paclitaxel therapy trial. Genome Med. 2021; 13: 11.
    OpenUrlPubMed
  23. 23.↵
    1. Li J,
    2. Qin S,
    3. Xu J,
    4. Xiong J,
    5. Wu C,
    6. Bai Y, et al.
    Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016; 34: 1448–54.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    1. Kawazoe A,
    2. Fukuoka S,
    3. Nakamura Y,
    4. Kuboki Y,
    5. Wakabayashi M,
    6. Nomura S, et al.
    Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020; 21: 1057–65.
    OpenUrlPubMed
  25. 25.
    1. Fukuoka S,
    2. Hara H,
    3. Takahashi N,
    4. Kojima T,
    5. Kawazoe A,
    6. Asayama M, et al.
    Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an open-label, dose-escalation, and dose-expansion phase Ib trial (REGONIVO, EPOC1603). J Clin Oncol. 2020; 38: 2053–61.
    OpenUrlCrossRefPubMed
  26. 26.
    1. Peng Z,
    2. Wei J,
    3. Wang F,
    4. Ying J,
    5. Deng Y,
    6. Gu K, et al.
    Camrelizumab combined with chemotherapy followed by camrelizumab plus apatinib as first-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma. Clin Cancer Res. 2021; 27: 3069–78.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Jiang H,
    2. Wang J,
    3. Deng W.
    Pathologic complete response to chemoimmunotherapy of an advanced gastric cancer patient with high PD-L1 expression, dMMR, and unique gut microbiota composition: a case report. Front Oncol. 2023; 13: 1150931.
  28. 28.↵
    1. Liao J,
    2. Jin H,
    3. Li S,
    4. Xu L,
    5. Peng Z,
    6. Wei G, et al.
    Apatinib potentiates irradiation effect via suppressing PI3K/AKT signaling pathway in hepatocellular carcinoma. J Exp Clin Cancer Res. 2019; 38: 454.
    OpenUrlPubMed
  29. 29.↵
    1. Choi B,
    2. Chun E,
    3. Kim M,
    4. Kim SY,
    5. Kim ST,
    6. Yoon K, et al.
    Human T cell development in the liver of humanized NOD/SCID/IL-2Rγnull(NSG) mice generated by intrahepatic injection of CD34+ human (h) cord blood (CB) cells. Clin Immunol. 2011; 139: 321–35.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Aryee KE,
    2. Burzenski LM,
    3. Yao LC,
    4. Keck JG,
    5. Greiner DL,
    6. Shultz LD, et al.
    Enhanced development of functional human NK cells in NOD-scid-IL2rgnull mice expressing human IL15. FASEB J. 2022; 36: e22476.
  31. 31.↵
    1. Kleinmanns K,
    2. Gullaksen SE,
    3. Bredholt G,
    4. Davidson B,
    5. Torkildsen CF,
    6. Grindheim S, et al.
    Humanized ovarian cancer patient-derived xenografts for improved preclinical evaluation of immunotherapies. Cancers (Basel). 2022; 14: 3092.
    OpenUrlPubMed
  32. 32.↵
    1. Weidner N.
    Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995; 36: 169–80.
    OpenUrlCrossRefPubMedWeb of Science
  33. 33.↵
    1. Nam HJ,
    2. Ching KA,
    3. Kan J,
    4. Kim HP,
    5. Han SW,
    6. Im SA, et al.
    Evaluation of the antitumor effects and mechanisms of PF00299804, a pan-her inhibitor, alone or in combination with chemotherapy or targeted agents in gastric cancer. Mol Cancer Ther. 2012; 11: 439–51.
    OpenUrlAbstract/FREE Full Text
  34. 34.↵
    1. Chung TD,
    2. Yu JJ,
    3. Kong TA,
    4. Spiotto MT,
    5. Lin JM.
    Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate. 2000; 42: 1–7.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Lu G,
    2. Tian S,
    3. Sun Y,
    4. Dong J,
    5. Wang N,
    6. Zeng J, et al.
    NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation. Theranostics. 2021; 11: 2460–74.
    OpenUrlPubMed
  36. 36.↵
    1. Nasir A,
    2. Holzer TR,
    3. Chen M,
    4. Man MZ,
    5. Schade AE.
    Differential expression of VEGFR2 protein in HER2 positive primary human breast cancer: potential relevance to anti-angiogenic therapies. Cancer Cell Int. 2017; 17: 56.
    OpenUrlPubMed
  37. 37.↵
    1. Klos KS,
    2. Wyszomierski SL,
    3. Sun M,
    4. Tan M,
    5. Zhou X,
    6. Li P, et al.
    ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006; 66: 2028–37.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Singh R,
    2. Kim WJ,
    3. Kim PH,
    4. Hong HJ.
    Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade. Exp Mol Med. 2013; 45: e52.
  39. 39.↵
    1. Lu K,
    2. Zhao Y,
    3. Li Y,
    4. Fu Z,
    5. Chen Y,
    6. Kong Y, et al.
    IFI16 promotes the progression of clear cell renal cell carcinoma through the IL6/PI3K/AKT axis. J Transl Med. 2024; 22: 533.
    OpenUrlPubMed
  40. 40.↵
    1. Dijkgraaf EM,
    2. Welters MJ,
    3. Nortier JW,
    4. van der Burg SH,
    5. Kroep JR.
    Interleukin-6/interleukin-6 receptor pathway as a new therapy target in epithelial ovarian cancer. Curr Pharm Des. 2012; 18: 3816–27.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Wang Y,
    2. Li L,
    3. Guo X,
    4. Jin X,
    5. Sun W,
    6. Zhang X, et al.
    Interleukin-6 signaling regulates anchorage-independent growth, proliferation, adhesion and invasion in human ovarian cancer cells. Cytokine. 2012; 59: 228–36.
    OpenUrlCrossRefPubMed
  42. 42.↵
    1. Vogt PK,
    2. Hart JR.
    PI3K and STAT3: a new alliance. Cancer Discov. 2011; 1: 481–6.
    OpenUrlAbstract/FREE Full Text
  43. 43.↵
    1. Sun Z,
    2. Jiang Q,
    3. Gao B,
    4. Zhang X,
    5. Bu L,
    6. Wang L, et al.
    AKT blocks SIK1-mediated repression of STAT3 to promote breast tumorigenesis. Cancer Res. 2023; 83: 1264–79.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Fukai S,
    2. Nakajima S,
    3. Saito M,
    4. Saito K,
    5. Kase K,
    6. Nakano H, et al.
    Down-regulation of stimulator of interferon genes (STING) expression and CD8+ T-cell infiltration depending on HER2 heterogeneity in HER2-positive gastric cancer. Gastric Cancer. 2023; 26: 878–90.
    OpenUrlPubMed
  45. 45.
    1. Loi M,
    2. Salvatore G,
    3. Sottili M,
    4. Calosi L,
    5. Desideri I,
    6. Becherini C, et al.
    Tumor-associated macrophages (TAMs) modulate response to HER2-targeted agents in a humanized mouse model of breast cancer. Clin Transl Oncol. 2022; 24: 1395–402.
    OpenUrlPubMed
  46. 46.↵
    1. Gong C,
    2. Lin Q,
    3. Cen Y,
    4. Fang X,
    5. Shi Y,
    6. Chen L, et al.
    Differences in tumor microenvironment between HER2-positive and HER2-negative breast cancer. J Clin Oncol. 2022; 40: e12562.
  47. 47.↵
    1. Huinen ZR,
    2. Huijbers EJM,
    3. van Beijnum JR,
    4. Nowak-Sliwinska P,
    5. Griffioen AW.
    Anti-angiogenic agents — overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat Rev Clin Oncol. 2021; 18: 527–40.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Shetty S,
    2. Weston CJ,
    3. Oo YH,
    4. Westerlund N,
    5. Stamataki Z,
    6. Youster J, et al.
    Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium. J Immunol. 2011; 186: 4147–55.
    OpenUrlAbstract/FREE Full Text
  49. 49.↵
    1. Yuan TL,
    2. Choi HS,
    3. Matsui A,
    4. Benes C,
    5. Lifshits E,
    6. Luo J, et al.
    Class 1A PI3K regulates vessel integrity during development and tumorigenesis. Proc Natl Acad Sci U S A. 2008; 105: 9739–44.
    OpenUrlAbstract/FREE Full Text
  50. 50.
    1. Vergadi E,
    2. Ieronymaki E,
    3. Lyroni K,
    4. Vaporidi K,
    5. Tsatsanis C.
    Akt signaling pathway in macrophage activation and M1/M2 polarization. J Immunol. 2017; 198: 1006–14.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    1. Crompton JG,
    2. Sukumar M,
    3. Roychoudhuri R,
    4. Clever D,
    5. Gros A,
    6. Eil RL, et al.
    Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2015; 75: 296–305.
    OpenUrlAbstract/FREE Full Text
  52. 52.↵
    1. Zhang Z,
    2. Richmond A,
    3. Yan C.
    Immunomodulatory properties of PI3K/AKT/mTOR and MAPK/MEK/ERK inhibition augment response to immune checkpoint blockade in melanoma and triple-negative breast cancer. Int J Mol Sci. 2022; 23: 7353.
    OpenUrlPubMed
  53. 53.
    1. Chandrasekaran S,
    2. Funk CR,
    3. Kleber T,
    4. Paulos CM,
    5. Shanmugam M,
    6. Waller EK.
    Strategies to overcome failures in T-cell immunotherapies by targeting PI3K-δ and -γ. Front Immunol. 2021; 12: 718621.
  54. 54.↵
    1. Zou S,
    2. Tong Q,
    3. Liu B,
    4. Huang W,
    5. Tian Y,
    6. Fu X.
    Targeting STAT3 in cancer immunotherapy. Mol Cancer. 2020; 19: 145.
    OpenUrlCrossRefPubMed
  55. 55.↵
    1. Mishra R,
    2. Foster DG,
    3. Finigan JH,
    4. Kern JA.
    Interleukin-6 is required for neuregulin-1 induced HER2 signaling in lung epithelium. Biochem Biophys Res Commun. 2019; 513: 794–9.
    OpenUrlPubMed
  56. 56.↵
    1. Hailemichael Y,
    2. Johnson DH,
    3. Abdel-Wahab N,
    4. Foo WC,
    5. Bentebibel SE,
    6. Daher M, et al.
    Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity. Cancer Cell. 2022; 40: 509–23.e6.
    OpenUrlCrossRefPubMed
  57. 57.↵
    1. Abdel-Wahab N,
    2. Montazari E,
    3. Spillson C,
    4. Bentebibel SE,
    5. Awiwi M,
    6. Elsayes KM, et al.
    Tocilizumab in combination with ipilimumab and nivolumab in solid tumors. J Clin Oncol. 2022; 40: TPS9600.
  58. 58.↵
    1. Tintelnot J,
    2. Paschold L,
    3. Goekkurt E,
    4. Schultheiss C,
    5. Matschl U,
    6. Santos Cruz M, et al.
    Inflammatory stress determines the need for chemotherapy in patients with HER2-positive esophagogastric adenocarcinoma receiving targeted therapy and immunotherapy. Cancer Immunol Res. 2025; 13: 200–9.
    OpenUrlPubMed
  59. 59.↵
    1. Boku N,
    2. Satoh T,
    3. Ryu MH,
    4. Chao Y,
    5. Kato K,
    6. Chung HC, et al.
    Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab. Gastric Cancer. 2021; 24: 946–58.
    OpenUrlCrossRefPubMed
  60. 60.↵
    1. Shitara K,
    2. Özguroglu M,
    3. Bang YJ,
    4. Di Bartolomeo M,
    5. Mandala M,
    6. Ryu MH, et al.
    Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018; 392: 123–33.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Lichtman SM,
    2. Wildiers H,
    3. Chatelut E,
    4. Steer C,
    5. Budman D,
    6. Morrison VA, et al.
    International society of geriatric oncology chemotherapy taskforce: evaluation of chemotherapy in older patients—an analysis of the medical literature. J Clin Oncol. 2007; 25: 1832–43.
    OpenUrlAbstract/FREE Full Text
  62. 62.↵
    1. Chen XL,
    2. Chen XZ,
    3. Yang C,
    4. Liao YB,
    5. Li H,
    6. Wang L, et al.
    Docetaxel, cisplatin and fluorouracil (DCF) regimen compared with non-taxane-containing palliative chemotherapy for gastric carcinoma: a systematic review and meta-analysis. PLoS One. 2013; 8: e60320.
  63. 63.↵
    1. Cordova-Delgado M,
    2. Bravo ML,
    3. Cumsille E,
    4. Hill CN,
    5. Muñoz-Medel M,
    6. Pinto MP, et al.
    A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer. BMC Cancer. 2021; 21: 1030.
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

Cancer Biology & Medicine: 23 (7)
Cancer Biology & Medicine
Vol. 23, Issue 7
15 Jul 2026
  • Table of Contents
  • Index by author
Print
Download PDF
Email Article

Thank you for your interest in spreading the word on Cancer Biology & Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Apatinib enhances targeted immunotherapy via the IL-6-gp130-PI3K pathway in HER2-positive gastric cancer
(Your Name) has sent you a message from Cancer Biology & Medicine
(Your Name) thought you would like to see the Cancer Biology & Medicine web site.
Citation Tools
Apatinib enhances targeted immunotherapy via the IL-6-gp130-PI3K pathway in HER2-positive gastric cancer
Ruoxi Tian, Ziyue Sha, Shasha Zhang, Miao Gong, Jianhua Wu, Juntao Lu, Wei Guo, Zhaoxu Zheng, Zhanjun Guo
Cancer Biology & Medicine Jul 2026, 20250687; DOI: 10.20892/j.issn.2095-3941.2025.0687

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Apatinib enhances targeted immunotherapy via the IL-6-gp130-PI3K pathway in HER2-positive gastric cancer
Ruoxi Tian, Ziyue Sha, Shasha Zhang, Miao Gong, Jianhua Wu, Juntao Lu, Wei Guo, Zhaoxu Zheng, Zhanjun Guo
Cancer Biology & Medicine Jul 2026, 20250687; DOI: 10.20892/j.issn.2095-3941.2025.0687
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and methods
    • Results
    • Discussion
    • Supporting Information
    • Conflict of interest statement
    • Author contributions
    • Data availability statement
    • References
  • Figures & Data
  • Info & Metrics
  • References
  • PDF

Related Articles

  • No related articles found.
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Psychological health mediates the association between diet and upper gastrointestinal cancer: a cross-sectional analysis from a large-scale population-based screening project
  • Lung cancer mortality trends in China from 2013 to 2021 and projections to 2030
  • Global landscape and temporal trends in lifetime risk of colorectal cancer in 185 countries: a population-based study
Show more Original Article

Similar Articles

Keywords

  • HER2
  • gastric cancer
  • apatinib
  • trastuzumab
  • targeted immunotherapy

Navigate

  • Home
  • Current Issue

More Information

  • About CBM
  • About CACA
  • About TMUCIH
  • Editorial Board
  • Subscription

For Authors

  • Instructions for authors
  • Journal Policies
  • Submit a Manuscript

Journal Services

  • Email Alerts
  • Facebook
  • RSS Feeds
  • Twitter

 

© 2026 Cancer Biology & Medicine

Powered by HighWire