HER-2 positive + HER-2 overexpression

P2, N=47, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

Our findings demonstrated a significant influence of HER2-low expression on the response to neoadjuvant chemotherapy among patients with hormone-positive HER2-low breast cancer within the studied cohort. Further studies are needed to evaluate the influence of hormonal expression on the response rate to NACT in the HER2-low patients in our population.

Despite the unfavorable prognosis associated with advanced GC, the implementation of personalized treatment approaches may still prove beneficial for select patients. In patients with HER2-positive GC with extensive metastatic involvement, the use of the HER2-targeted combination with apatinib has demonstrated the potential to prolong both PFS and overall survival.

The radiomic signature and tumor descriptors from gray-scale US may predict distinct HER2 expressions of breast cancers with therapeutic implications.

In this study, we focused on differences in the TME between HER2-positive and HER2-negative areas in HER2-positive GC and found that HER2 signaling, particularly the HER2-Akt cascade, may suppress stimulator of interferon genes (STING)expression and reduce CD8+ T cell infiltration in tumor cells. Overall, our findings suggest the potential for a novel therapeutic approach to activate the anti-tumor immune response in HER2-positive GC.

To overcome these obstacles, we have engineered cyclic Arg-Gly-Asp (cRGD)-modified red blood cell membrane (RBCm)-coated multidrug nanocomplexes, which were self-assembled from the Polo-like kinase 1 siRNA (siPlk1) and an irreversible tyrosine kinase inhibitor neratinib targeted to human epidermal growth factor receptor 2 (HER2) overexpressed in breast cancer...The cRGD-modified red blood cell membranes coated on the surface of the multidrug nanoparticles could enhance drug stability in circulation and tumor accumulation. This targeted combinational therapy significantly enhanced the antitumor efficiency in HER2-positive breast cancer in vitro and in vivo.

Background: Trastuzumab resistance is associated with overexpressing the human epidermal growth factor receptor 2 (HER-2), which results from the altered phosphoinositide 3-kinase (PI3K) pathway in breast cancer patients...However, single and double-point mutations in PI3K were significantly associated with the clinical stages of diagnosis and tumor size (p = 0.027 and p = 0.04, respectively). Single and double-point mutations in PI3K are related to tumor size and advanced clinical-pathological traits in Mexican patients with HER-2 overexpression, and future molecular studies are necessary to understand these findings.

Knockdown of EGFR expression or pharmacologic stimulation of EGFR endocytosis with EGFR monoclonal antibodies restores T-DXd trafficking and antitumor activity in EGFR-overexpressing cancers in vivo. Our results reveal EGFR overexpression to be a potential mechanism of resistance to T-DXd, which can be overcome by combination therapy strategies targeting EGFR.

A quarter of high-risk, metastatic, or recurrent EC exhibited HER2 overexpression. The presence of HER2 overexpression in all clinical and molecular categories highlights the need for broad testing and offers treatment options for a wide range of patients.

Administration of NPs-T-DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T-DM1-induced thrombocytopenia, and remarkably improves the safety of antibody-conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T-DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2-positive breast cancer patients.

The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

P1/2, N=52, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Apr 2025 --> Sep 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

As a novel survival biomarker in gastric cancer, HER2 overexpression indicates unfavorable prognosis among both resectable and advanced patients, irrespective of East Asian or non-East Asian populations. PROSPERO (CRD42020168051).

We concluded that HER2 signals through the RIP signaling pathway that promotes cell proliferation and is targeted by trastuzumab. The aberrant HER2 RIP signaling confers resistance to trastuzumab that could be overcome by the application of inhibitors to ADAM10 and γ-secretase.

Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future.

This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.

We found that patients with HER2-high disease were more likely to achieve pCR after NAT compared to patients with HER2-intermediate BC, a subgroup of patients that may benefit from more personalized NAT strategies.

Our study highlights the variable expression and significance of HER2 testing across multiple solid tumor types, reinforcing the importance of HER2 testing to optimize the utilization of T-Dxd in the real-world setting.

Although p53abn ECs are clinically aggressive, these tumours may present different molecular features as HER2 overexpression/amplification. Anti-HER2 target therapy represents a new therapeutic option. HER2-positive carcinomas represent a subgroup of tumours characterized by distinct histological features, although without significant prognostic impact.