Ask about this productRelated genes to: HER2 protein
- Gene:
- ERBB2 NIH gene
- Name:
- erb-b2 receptor tyrosine kinase 2
- Previous symbol:
- NGL
- Synonyms:
- NEU, HER-2, CD340, HER2
- Chromosome:
- 17q12
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2019-04-23
Related products to: HER2 protein
Related articles to: HER2 protein
- : Precise intracellular delivery of chemotherapeutics remains a major challenge in HER2-positive breast cancer, where intratumoral heterogeneity and limited tissue penetration constrain efficacy. A key contributor is the tumor-restricted epidermal growth factor receptor variant III (EGFRvIII), a constitutively active, ligand-independent mutant generated by deletion of exons 2-7. Although classically associated with glioblastoma, lung (NSCLC), head/neck, and prostate cancers, EGFRvIII is also present in subsets of HER2-positive breast cancers, where low-abundance subclones drive aggressive phenotypes and attenuate therapeutic responses. HER2-EGFRvIII co-expression amplifies oncogenic signaling, supported by frequent co-expression in ErbB2-positive primary tumors and metastases, and by sustained receptor phosphorylation in the absence of EGFR gene amplification, depicting EGFRvIII as a compelling therapeutic target. : We evaluated the shark-derived single-domain antibody vNAR R426 as a modular theranostic platform for receptor-mediated cisplatin delivery. Conjugation to cisplatin and fluorescein enabled simultaneous intracellular drug transport and immunofluorescence-based detection in EGFRvIII-positive SKBR3 cells and 3D spheroids. The compact vNAR-based immunoconjugates support efficient receptor recognition, internalization, and intracellular trafficking, features rarely achieved by conventional IgG antibodies. : vNAR elicited robust, receptor-mediated cytotoxicity, achieving an IC of 2.68 µM-approximately 50-fold lower than that of free cisplatin-while unconjugated vNAR maintained scaffold biocompatibility. In three-dimensional spheroid models, the theranostic vNAR (vNAR) exhibited deep and uniform penetration throughout tumor-like architectures, with immunofluorescence intensity closely correlating with regions of intracellular drug delivery and the initiation of cytotoxic responses. Notably, cisplatin conjugation did not impair tissue diffusion or receptor engagement, facilitating effective payload delivery to both peripheral and central cell populations. : By integrating tumor-restricted targeting and efficient intracellular drug delivery within a modular single-domain scaffold, vNAR R426 represents a next-generation theranostic platform capable of addressing intratumoral heterogeneity. This approach combines potent cytotoxic activity with immunofluorescence-based detection, thereby advancing the rational design of precision therapeutics for HER2-positive breast cancer. - Source: PubMed
Publication date: 2026/04/17
Alfonseca-Ladrón de Guevara Andrea CManzanares-Guzmán AlejandroBadillo-Mata Jessica ABurciaga-Flores MirnaLugo-Fabres Pavel HCamacho-Villegas Tanya A - HER2-low breast cancer, also known as IHC 1+ or IHC 2+ without ERBB2 amplification, is a new concept in the biology of breast cancer that has removed the binary classification of HER2-positive or HER2-negative breast cancer. The recent introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd), has improved therapeutic outcomes for HER2-low breast cancer by demonstrating high efficacy in HER2-low tumors through efficient payload delivery. However, differences in ADC efficacy exist among HER2-low breast cancer patients, with tumor cells showing resistance to ADCs. Recent research indicates that the tumor microenvironment (TME) plays a critical role in determining the efficacy of ADCs against tumor cells. TME creates a barrier to the delivery of ADCs to tumor cells that show resistance to ADCs. This review article aims to highlight the current understanding of the biology of HER2-low breast cancer and its response to ADCs with reference to the tumor microenvironment. - Source: PubMed
Publication date: 2026/03/27
Basem YoussefAta AlamerSherif AbanoubAbdel-Ghany ShaimaaArneth BorrosSabit Hussein - : Neoadjuvant systemic therapy incorporating dual HER2 blockade has significantly improved outcomes in patients with HER2-positive breast cancer. Pathological complete response (pCR) is an important surrogate endpoint associated with improved long-term survival. However, substantial heterogeneity in treatment response persists, and identifying factors associated with pCR remains clinically relevant. In addition to established clinicopathological variables, systemic inflammation-based biomarkers have recently been investigated as potential predictors of treatment response. : In this multicenter retrospective study, we evaluated patients with stage II-III HER2-positive breast cancer who received pertuzumab-based neoadjuvant therapy followed by surgery between January 2023 and June 2025 across six oncology centers in Türkiye. Clinicopathological characteristics, treatment-related variables, and baseline systemic inflammation-based biomarkers were analyzed. Logistic regression analyses were performed to identify factors associated with pCR. : A total of 372 patients were included, and the overall pCR rate was 61%. Higher pCR rates were observed in patients with hormone receptor-negative tumors (71.4% vs. 54.3%, = 0.001) and in premenopausal patients (68.7% vs. 53.4%, = 0.003). In multivariate analysis, hormone receptor status (OR 2.25, 95% CI 1.41-3.60, < 0.001), menopausal status (OR 1.90, 95% CI 1.22-2.94, = 0.005), neoadjuvant treatment regimen (OR 2.15, 95% CI 1.05-4.41, = 0.037), and perineural invasion (OR 2.61, 95% CI 1.10-6.22, = 0.030) were independently associated with pCR. In contrast, systemic inflammation-based biomarkers did not demonstrate significant associations with pCR, and ROC analyses showed limited discriminatory ability (AUC values approximately 0.5). : In patients with HER2-positive breast cancer treated with pertuzumab-based neoadjuvant therapy, treatment response appears to be primarily influenced by clinicopathological and treatment-related factors rather than systemic inflammatory status. Peripheral blood inflammatory biomarkers derived from routine laboratory parameters showed limited value in predicting pCR in this setting. - Source: PubMed
Publication date: 2026/04/15
Yıldız FatihKarabuga BerkanKaratlı SalihYalınkılıç MerveDeliktas Onur İlknurBilgic Koylu EceSoylu Kocoğlu SılaEraslan EmrahIlhan Gülesen AysegülErdur ErkanYildirim Ozgen AhmetGurler FatihYasar Hatime ArzuAslan Ferit - : Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are recommended as first- or second-line treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or recurrent breast cancer. However, in clinical practice, initiation timing varies according to patient characteristics, prior treatments, and the choice of the physician. Thus, the optimal timing of combination treatment remains unclear. : In this multicenter retrospective cohort study, we reviewed 66 female patients who received CDK4/6i (palbociclib or abemaciclib) between March 2018 and November 2019. Patients were categorized into the first-line treatment (group A) ( = 21) and second- or subsequent-line treatment (group B) ( = 45) groups. In the latter group, endocrine therapy and/or chemotherapy had been administered previously. Duration of treatment with CDK4/6i (DOT), overall survival (OS), treatment duration of other regimens, and reasons for treatment discontinuation after CDK4/6i treatment were compared between groups. : The median DOT was significantly longer in group A than in group B (23 months (95% CI, 8-43) vs. 7 months (95% CI, 3-15); = 0.015, at log-rank test). OS showed no significant difference between the two groups ( = 0.69, at log-rank test). : In patients with HR-positive, HER2-negative advanced or recurrent breast cancer, first-line use of CDK4/6 inhibitors was associated with a significantly longer duration of treatment compared with second- or subsequent-line use. However, no significant difference in OS was observed between patients receiving CDK4/6 inhibitors as first-line or second- or subsequent-line therapy. - Source: PubMed
Publication date: 2026/03/31
Yao ShokoImoto ShigeruTsuchiya AiIsaka HirotsuguSeki HirohitoAsaga SotaYokoi ShigehiroKoneri KenjiMaeda HiroyukiGoi Takanori - Vitamin D is a secosteroid that exerts immunomodulatory and anti-proliferative effects through the vitamin D receptor (VDR). Because HER2-targeted therapies substantially improve prognosis in HER2-positive breast cancer and introduces a new mechanism of immunotherapy, we hypothesized that successful correction of vitamin D deficiency would be associated with improved disease-free survival (DFS) in patients treated with curative intent. - Source: PubMed
Publication date: 2026/04/16
Ahn Eugene RIyer NandhiniCothran Samuel B