Research Advances in the Use of Trastuzumab for Advanced Gastric Cancer Treatment

DOI: https://doi.org/10.62517/jmhs.202605227

Author(s)

Yanyue Sun

Affiliation(s)

School of Life Sciences, Qufu Normal University, Qufu, Shandong, China

Abstract

Gastric cancer ranks among the most prevalent malignant tumors globally, with advanced-stage patients exhibiting extremely poor prognosis and limited efficacy from traditional treatments. Trastuzumab, as the first targeted therapy against human epidermal growth factor receptor 2 (HER2), has fundamentally transformed the treatment landscape for HER2-positive advanced gastric cancer. This systematic review examines trastuzumab's mechanism of action, current clinical applications, resistance mechanisms, and recent breakthroughs. It focuses on analyzing clinical research advances in recent years regarding monotherapy and combination therapies with immunotherapy, chemotherapy drugs, and dual-targeted treatments. The review explores strategies to overcome resistance and future development directions. Research indicates that trastuzumab combination therapy has become the standard treatment regimen for HER2-positive advanced gastric cancer. Furthermore, the in-depth analysis of novel combination strategies and resistance mechanisms provides crucial support for further enhancing therapeutic efficacy.

Keywords

Trastuzumab; HER2-Positive; Targeted Therapy; Resistance Mechanisms; Combination Therapy

References

[1] Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394–424. [2] Bang, Y. J., Van Cutsem, E., Feyereislova, A., Chung, H. C., Shen, L., Sawaki, A. (2010). 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. The Lancet, 376(9742), 687–697. [3] Yarden, Y., Sliwkowski, M. X. (2001). Untangling the ErbB signalling network. Nature Reviews Molecular Cell Biology, 2(2), 127–137. [4] Clynes, R. A., Towers, T. L., Presta, L. G., Ravetch, J. V. (2000). Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nature Medicine, 6(4), 443–446. [5] Nahta, R., Hung, M. C., Esteva, F. J. (2006). Mechanisms of trastuzumab resistance. Breast Cancer Research, 8(3), 215. [6] Xue, C., Xu, Y.-H. (2022) Trastuzumab combined chemotherapy for the treatment of HER2-positive advanced gastric cancer: A systematic review and meta-analysis of randomized controlled trial. Medicine, 101: e29992. [7] Smyth, E.C., Nilsson, M., Grabsch, H.I., van Grieken, N.C., Lordick, F. (2020) Gastric cancer. Lancet, 396: 635–648. [8] Janjigian, K. N., Shitara, K., Muro, K., Van Cutsem, E., Bang, Y. J., Fuchs, C. S. (2023). Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma: final analysis of the phase 3 KEYNOTE-811 trial. Annals of Oncology, 34(10), 895–904. [9] Shitara, K., Bang, Y. J., Iwasa, S., Sugimoto, N., Ryu, M. H., Sakai, D. (2021). Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. The New England Journal of Medicine, 384(25), 2419–2430. [10] Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S. (2004). High frequency of mutations of the PIK3CA gene in human cancers. Science, 304(5670), 554. [11] Kalluri, R., Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. The Journal of Clinical Investigation, 119(6), 1420–1428. [12] Woo, S. R., Turnis, M. E., Goldberg, M. V., Bankoti, J., Selby, M., Nirschl, C. J. (2012). Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Research, 72(4), 917–927. [13] Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Medicine, 8(8), 793–800. [14] Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. The New England Journal of Medicine, 366(26), 2443–2454. [15] Modi, S., Saura, C., Yamamoto, T., Andre, F., Park, Y. H., Kim, S. B. (2020). Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. The New England Journal of Medicine, 382(7), 610–621.