Emerging insights into mechanisms of trastuzumab resistance in HER2-positive cancers

Wu, Xiaoxue; Huang, Shuting; He, Weiling; Song, Mei

doi:10.1016/j.intimp.2023.110602

Cited by 6 publications

(2 citation statements)

References 184 publications

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“…By binding to HER2, trastuzumab reduces the formation of homodimers and impedes growth signal transduction, effectively inhibiting the progression of BC [15] . However, some patients do not show long-term benefits from trastuzumab therapy [16] .…”

Section: Discussionmentioning

confidence: 99%

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

Li,

Wu,

Shi

et al. 2024

ABBS

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Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is characterized by high invasiveness. Trastuzumab considerably improves the prognoses of HER2-positive BC, but some patients exhibit drug resistance. In this study, the effects of XLLXF combined with trastuzumab on the proliferation, apoptosis, invasion, and migration of HER2-positive BC cells are evaluated, and network pharmacology is performed. Then, we conduct an in vivo study using a xenograft mouse model of HER2-positive BC, and tumor growth is monitored. The expression levels of cytokines are measured by ELISA. Molecular docking is performed to observe the binding stability of IL2, JAK, STAT, and TNF with curcumenol, icariside-II, lobetyolin, and scutellarein. Finally, we observe changes in JAK1 and TNF-α in tumor tissues by immunohistochemistry. The results show that XLLXF enhances the inhibitory effects of trastuzumab on the proliferation, colony formation ability, migration, and invasion of HER2-positive BC cells and promotes apoptosis. Network pharmacology reveals that XLLXF may exert its effects on HER2-positive BC by modulating pathways such as the ErbB, JAK-STAT, and NF-κB pathways. Potential targets include cytokines closely related to immune function. In the in vivo study, XLLXF synergistically enhances the inhibitory effects of trastuzumab on tumor growth. ELISA reveals that XLLXF combined with trastuzumab increases the levels of IL-15, IL-2, TNF-α, and IFN-γ in tumor-bearing mice. Immunohistochemistry confirms that XLLXF can regulate the expressions of JAK1 and TNF-α. This study demonstrates that XLLXF can synergistically enhance the efficacy of trastuzumab in targeting HER2-positive BC. The mechanism may involve the modulation of inflammatory factors.

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Section: Discussionmentioning

confidence: 99%

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

Li,

Wu,

Shi

et al. 2024

ABBS

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“…Each of these alterations could presents an intriguing opportunity for therapeutic intervention to be explored in dedicated clinical trials. PI3K inhibitors, mTOR inhibitors, and various endocrine therapies could emerge as valuable tools that can be harnessed to specific therapeutic targets [107].…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Targeted Therapy in Solid Cancers: Pioneers and New Glories

Sposito,

Belluomini,

Pontolillo

et al. 2023

JPM

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Targeted therapy (TT) has revolutionized cancer treatment, successfully applied in various settings. Adjuvant TT in resected early-stage gastrointestinal stromal tumors (GIST), melanoma, non-small cell lung cancer (NSCLC), and breast cancer has led to practice-changing achievements. In particular, standard treatments include BRAF inhibitors for melanoma, osimertinib for NSCLC, hormone therapy or HER2 TT for breast cancer, and imatinib for GIST. Despite the undeniable benefit derived from adjuvant TT, the optimal duration of TT and the appropriate managing of the relapse remain open questions. Furthermore, neoadjuvant TT is emerging as valuable, particularly in breast cancer, and ongoing studies evaluate TT in the perioperative setting for early-stage NSCLC. In this review, we aim to collect and describe the large amount of data available in the literature about adjuvant TT across different histologies, focusing on epidemiology, major advances, and future directions.

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Targeting HER2 in solid tumors: Unveiling the structure and novel epitopes

Liu,

Song,

Cheng

et al. 2024

Cancer Treatment Reviews

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Emerging insights into mechanisms of trastuzumab resistance in HER2-positive cancers

Cited by 6 publications

References 184 publications

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

Adjuvant Targeted Therapy in Solid Cancers: Pioneers and New Glories

Targeting HER2 in solid tumors: Unveiling the structure and novel epitopes

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Emerging insights into mechanisms of trastuzumab resistance in HER2-positive cancers

Cited by 6 publications

References 184 publications

&lt;italic&gt;Xianling Lianxia&lt;/italic&gt; formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

&lt;italic&gt;Xianling Lianxia&lt;/italic&gt; formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

Adjuvant Targeted Therapy in Solid Cancers: Pioneers and New Glories

Targeting HER2 in solid tumors: Unveiling the structure and novel epitopes

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Product

Resources

About

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer