Molecular mechanism of XB130 adaptor protein mediates trastuzumab resistance in gastric cancer

Yang, Shengnan; Wang, Binbin; Liao, Jiaqi; Hong, Ziyang; Zhong, Xuxian; Chen, Suling; Wu, Ziqing; Zhang, Xingyu; Zuo, Qiang

doi:10.1007/s12094-022-02974-w

Cited by 1 publication

(1 citation statement)

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“…PTEN loss is associated with primary resistance to trastuzumab and represents a negative prognostic factor [56]. Other mechanisms of PI3K activation and mediating trastuzumab resistance include the upregulation of NES1/KLK10, the protooncogene XB130 or the c-MET-associated MACC1 [57][58][59]. As a response to trastuzumab, the HER3 ligand heregulin (or neuregulin1β) is released by the metalloprotease ADAM 10 and mediates resistance to HER2-targeting agents.…”

Section: Resistance To Trastuzumabmentioning

confidence: 99%

HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments

Scheck,

Hofheinz,

Lorenzen

2024

Cancers

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Despite a decreasing incidence in Western countries, gastric cancer is among the most common cancer subtypes globally and is associated with one of the highest tumor-related mortality rates. Biomarkers play an increasing role in the treatment against gastric cancer. HER2 was one of the first biomarkers that found its way into clinical practice. Since the ToGA trial, trastuzumab has been part of first-line palliative chemotherapy in metastatic or unresectable gastric cancer. HER2-targeting agents, such as the tyrosine kinase inhibitor lapatinib, the antibody drug conjugate (ADC) trastuzumab-emtansine or dual HER2 inhibition (pertuzumab and trastuzumab), have been investigated in the second-line setting but led to negative study results. More recently, the ADC trastuzumab-deruxtecan was authorized after the failure of trastuzumab-based treatment. However, further improvements in HER2-directed therapy are required as resistance mechanisms and HER2 heterogeneity limit the existing treatment options. This review aims to give an overview of the current standard-of-care HER2-directed therapy in gastric cancer, as well as its challenges and future developments.

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