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trastuzumab (HS 022 / HS022 / anruize)

✓ Approved

BioRay Pharmaceutical · ERBB2 · 单克隆抗体

什么是 trastuzumab？

trastuzumab 是一种单克隆抗体，由BioRay Pharmaceutical研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

商品名HS 022, HS022, anruize
公司BioRay Pharmaceutical
药物类别单克隆抗体, 抗体
分子靶点ERBB2
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, BioRay Pharmaceutical

作用机制

分子靶点

trastuzumab 作用于 1 个分子靶点：

ERBB2erb-b2 receptor tyrosine kinase 2 (NEU, CD340)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

trastuzumab 针对 2 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancer✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Gastric cancer✓ Approved

相关研究文献

PubMedCancer medicine2026-07-27

A Phase I/II Study of Ibrutinib Plus Trastuzumab in HER2-Positive Metastatic Breast Cancer.

O'Shaughnessy Joyce J, Glidden Andrea A, Locke Tracy T, Scales Amy A et al.

Ibrutinib has demonstrated inhibition of ErbB/HER tyrosine kinases in preclinical models. This Phase I/II study investigated the safety, efficacy, and immunomodulatory effects of ibrutinib in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on ado-trastuzumab emtansine therapy. In Phase I, cohorts of three patients received ibrutinib 560 mg or 420 mg by mouth once daily combined with standard dosing of trastuzumab. Phase II enrolled additional patients to assess the primary endpoint of clinical benefit rate (CBR) at 420 mg ibrutinib plus trastuzumab. Flow cytometry and NanoString analyses were performed on peripheral blood mononuclear cells. Overall, 26 patients were enrolled. Patients received a median of three prior regimens containing a HER2-targeted therapy in any setting. The most common treatment-related adverse events were bruising, rash, fatigue, and thrombocytopenia. Four patients (15%) experienced cardiac adverse events, including decreased left ventricular ejection fraction in two patients. The CBR of ibrutinib plus trastuzumab was 19.2% (95% confidence interval: 6.6-39.4). Flow cytometry of T- and natural killer (NK)-cell and myeloid-cell panels showed that treatment statistically significantly decreased T helper 17 (TH17) and myeloid-derived suppressor cells (MDSC) with no decrease in T helper 2 (TH2) cells. Ibrutinib plus trastuzumab was well-tolerated but had limited anti-tumor activity in patients with heavily pretreated, HER2-positive MBC (NCT03379428). Trial Registration: Clinicaltrials.gov, NCT03379428.

PMID 42504645
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PubMedNaunyn-Schmiedeberg's archives of pharmacology2026-07-27

Cycloastragenol overcomes trastuzumab resistance in HER2-positive breast cancer by regulating cell cycle and epithelial-mesenchymal transition through EZH2/PTEN/AKT pathway.

Wu Mingyuan M, Hou Fenggang F, Yang Zhaoshuo Z, Zhu Zhenfeng Z et al.

The resistance of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients to trastuzumab (Tmab) severely restricts its efficacy. As a natural metabolite with antitumor activity, whether cycloastragenol (CAG) can overcome Tmab resistance and its related mechanism are not clear. This study aims to verify if CAG reverses Tmab resistance in HER2-positive breast cancer cells, clarify its regulatory effects on resistant cell behaviors, and explore the role of the EZH2/PTEN/AKT axis. The study design is combined in vivo and in vitro study. The BT474-TR cells were constructed, and HER2 expression was detected by Western blot and immunofluorescence. Cell Counting Kit-8 assay served to screen the optimal CAG concentration and Tmab dosage. Cell proliferation, migration, and invasion capabilities were evaluated via CFSE staining, colony formation assay, and Transwell and scratch assays. Flow cytometry was employed to examine apoptosis and cell cycle arrest. A xenograft tumor model was established in nude mice. Pathological changes were observed via HE staining, apoptosis was detected using TUNEL staining, microvascular density and VEGF levels were assessed by immunohistochemistry, and protein expression was validated by Western blot. Tmab reduced BT474-TS cell viability and downregulated HER2, while exhibiting minimal effects on HER2-high expression BT474-TR and JIMT-1 cells. CAG treatment enhanced the efficacy of Tmab against drug-resistant cells, reducing cell viability and proliferation, promoting apoptosis, and inducing G0/G1 phase cycle arrest. CAG suppressed migration and invasion capabilities while reversing the EMT phenotype. Additionally, CAG downregulated EZH2 and p-AKT while upregulating PTEN; overexpression EZH2 diminished CAG's antitumor activity. Following CAG combined with Tmab treatment, tumor volume and weight in nude mice were smaller, and tumor tissue exhibited increased pathological damage, elevated apoptotic cells, and reduced microvascular density and VEGF levels. CAG modulates the cell cycle and EMT through the EZH2/PTEN/AKT pathway, effectively overcoming Tmab resistance in HER2-positive BC cells. Clinical trial number: Not applicable.

PMID 42507167
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PubMedBreast (Edinburgh, Scotland)2026-07-26

Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases.

Grinda Thomas T, Heiling Hillary M HM, Tayob Nabihah N, Smith Karen L KL et al.

In TBCRC 022 (NCT01494662), neratinib and ado-trastuzumab emtansine (T-DM1) demonstrated intracranial activity among patients with HER2-positive breast cancer brain metastases. However, gastrointestinal (GI) toxicities-particularly diarrhea-were common, potentially impacting quality of life. Clinician-reported adverse event (CTCAE) grading may underestimate the patient experience. We report GI toxicities using patient-reported outcomes (PROs) in TBCRC's neratinib-T-DM1 cohort. Patients received neratinib (160 mg daily) and T-DM1 (3.6 mg/kg IV every 21 days). A pre-planned analysis assessed patient-reported GI toxicities during Cycles 1-4 using the Patient-reported Outcomes Measurement Information System (PROMIS) GI Diarrhea scale, Systemic Therapy-Induced Diarrhea Assessment Tool (STIDAT), and PRO-CTCAE. Descriptive statistics and linear mixed effects models evaluated symptom trajectories over time. We evaluated agreement for PRO and clinician-reported data. Forty-four patients enrolled; all completed ≥1 PRO. GI symptom burden increased over Cycles 1-3. PROMIS scores worsened significantly by Cycle 2, with a peak mean increase of 6.62 (95% confidence interval (CI): 2.67-10.59; p = 0.002) at Cycle 3. STIDAT scores also worsened by Cycle 3 (mean change 0.50; 95%CI: 0.11-0.90; p = 0.015). Based on maximum PRO-CTCAE scores, moderate-to-severe symptoms were reported by 20.5% (diarrhea), 24.4% (appetite loss), and 41.0% (constipation). Agreement between PRO-CTCAE and clinician-reported CTCAE was low (kappa <0.2) with clinicians reporting less toxicity. PROMIS and STIDAT scores were significantly correlated. This GI-focused PRO analysis highlights the value of PROs in capturing patient-experienced toxicities that impact quality of life yet are underestimated by clinicians. Incorporating PROs into clinical trials can inform supportive care and prophylactic strategies.

PMID 42501479
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PubMedOncology research2026-07-25

Research Advances in Drug Resistance Mechanisms to Anti-HER2 Therapy in HER2-Positive Breast Cancer.

Huang Chunwei C, Kong Jingyi J, Ren Hangxing H, Zhang Wanchen W et al.

HER2-positive breast cancer accounts for 15-20% of all breast cancer cases. Although the development of monoclonal antibodies (e.g., trastuzumab, pertuzumab), tyrosine kinase inhibitors (e.g., lapatinib, pyrotinib), and antibody-drug conjugates (e.g., T-DM1, trastuzumab deruxtecan) has greatly improved patient prognosis, primary or acquired resistance to anti-HER2 therapy remains a major clinical challenge, leading to treatment failure and disease progression. Recent research has elucidated diverse resistance mechanisms, including HER2 signaling pathway aberrations (such as receptor mutations, alternative splicing, and bypass activation), tumor microenvironment remodeling (involving immunosuppressive cells, metabolic reprogramming, and immune checkpoint molecules), and ADC-specific resistance (impaired internalization, lysosomal dysfunction, payload efflux, and ferroptosis blockade). However, existing reviews primarily focus on trastuzumab and classical signaling pathways, with insufficient integration of ADC-specific mechanisms or microenvironmental immune evasion. Furthermore, the translation of mechanistic discoveries into clinical strategies remains weak, and a systematic summary of validated biomarkers (e.g., PIK3CA mutations, PTEN loss, p95HER2, ADAR1, HLA-G) and related clinical trials is lacking. The purpose of this review is threefold: (1) to systematically integrate recent advances in anti-HER2 resistance mechanisms from three perspectives-HER2 signaling abnormalities, tumor microenvironment remodeling, and ADC-specific barriers; (2) to provide an evidence-based framework for target prioritization by categorizing mechanisms according to their validation stage (clinically validated, substantial in vivo evidence, or in vitro studies only); and (3) to summarize current biomarker-driven clinical trials and emerging therapeutic strategies, including combination immunotherapy, CDK4/6 inhibitors, PI3K PROTACs, and cold atmospheric plasma. Ultimately, this review aims to bridge the gap between basic research and clinical practice, offering practical guidance for overcoming anti-HER2 resistance through precision combination strategies in HER2-positive breast cancer.

PMID 42500590
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PubMedGynecologic oncology reports2026-07-25

Preclinical in vitro and in vivo activity of trastuzumab deruxtecan against ERBB2-mutated cervical carcinomas with low HER2 expression.

Sethi Namrata N, Ottum Sarah S, Bellone Stefania S, Demirkiran Cem C et al.

Somatic HER2 mutations occur in up to 6% of cervical cancer patients and are associated with poor prognosis. We explored the activity of trastuzumab deruxtecan (T-DXd) as a novel targeted therapy against HER2-mutated primary cervical cancer cell lines and xenografts with low HER2 expression. HER2 expression was assessed by flow cytometry, while ERBB2 mutations were identified by whole-exome sequencing. Cytotoxicity was measured by flow cytometry-based viability assays, and double-stranded DNA breaks were evaluated using anti-phosphorylated-histone H2AX antibody. Bystander effect was assessed by co-culturing HER2-S310F-mutated (CVX4) and non-mutated (CVX8) tumor cells. In vivo, efficacy was tested over 47 days in severe combined immunodeficient mice bearing CVX4-xenografts (n = 4 in each group). All eight primary cell lines available demonstrated low HER2 expression. CVX4 (HER2-S310F activating mutation) was significantly more sensitive to T-DXd than control antibody-drug conjugate (CTL-ADC) as demonstrated in the cytotoxicity experiments (p = 0.0036) and double-stranded DNA break assays (p = 0.0057). CVX3, a tumor with a HER2 mutation of unknown significance (HER2-E405D) and CVX8 (HER2-non-mutated) showed no difference in sensitivity to the ADC. T-DXd induced substantial bystander killing in the co-culture (p = 0.0223) while in vivo, a single retroorbital injection of T-DXd (4 mg/kg) was well tolerated and achieved remarkable growth inhibition compared with CTL-ADC in CVX4-xenografts (p < 0.0001). T-DXd was shown to be highly active against HER2-S310F-mutated cervical cancer cell lines and xenografts. T-DXd may represent a novel, effective therapeutic option for recurrent cervical cancer patients harboring mutations in the ERBB2 gene, regardless of low HER2 expression.

PMID 42500114
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PubMedCureus2026-07-25

Synchronous HER2-Positive Breast and Gastric Cancers: A Dual Diagnostic Challenge With a Single Treatment Possibility.

Morka Jeremi J, Biernat Paula P, Czerwinska Anna A, Cybulska Klaudia K et al.

Synchronous primary malignancies are rare and represent a significant diagnostic and therapeutic challenge, particularly when both tumors share a targetable molecular alteration. We present a case of synchronous human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers treated using a common HER2-directed strategy. A 77-year-old female was admitted with a right breast lesion classified as Breast Imaging Reporting and Data System (BI-RADS) 5. A core needle biopsy was performed, which confirmed a grade 2 invasive ductal carcinoma. The results showed positivity for estrogen receptor and progesterone receptor, a HER2 immunohistochemical score of 2+, and a Ki-67 index of 15%. Chromogenic in situ hybridization (CISH) confirmed HER2 amplification, establishing a luminal B/HER2-positive subtype (cT4b cN0 cM0). The patient was started on a course of tamoxifen treatment. During the course of treatment, there was a progression of dysphagia and rapid weight loss, which prompted further investigation. A CT scan revealed thickening of the gastric cardia. Following the failure of gastroscopies due to esophageal stenosis, exploratory laparoscopy was performed. The histopathological examination revealed that the gastric cardia tumor was grade 1 tubular adenocarcinoma, with HER2 overexpression (immunohistochemistry (IHC) 3+), proficient mismatch repair (pMMR)/microsatellite stability (MSS) status, and no hormone receptor expression. Due to the unresectable nature of the disease, the patient received a combination of palliative mFOLFOX6 (leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin) and trastuzumab, in addition to ongoing endocrine therapy. Following four cycles, imaging showed disease stabilization, with decreased cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) levels, and evidence of local tumor regression. Despite an initial positive response, the patient subsequently experienced disease progression and clinical deterioration after three months. The overall survival rate was 11.25 months. This case demonstrates the importance of comprehensive molecular diagnostics and the potential of HER2-targeted therapy as a unified treatment approach for synchronous HER2-positive malignancies.

PMID 42500763
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