HER-2 overexpression

Within NSCLC, 26% of activating mutations were not included in clinical trials that led to approval of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd)...We identified substantial populations of patients with diverse ERBB2/ERBB3 activating alterations, which represent unmet therapeutic needs. We demonstrate that CGP provides additional genomic information, inclusive of ERBB2 amplification and mutation status together with potential resistance/response-modifying co-alterations, allowing for more nuanced HER2 status interpretation than is possible with IHC/FISH alone.

Although the addition of modified FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to active symptom control improved the overall survival of patients with progressing advanced BTC despite gemcitabine plus cisplatin treatment, its efficacy was modest. This review delineates the evolution of systemic therapies in patients with pretreated advanced BTC. By examining past developments and recent advances through prospective trials, it highlights novel approaches that may improve outcomes in this challenging disease.

P4, N=500, Recruiting, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; Pierre Fabre (Shanghai) Medical Co.,Ltd.

P2, N=20, Not yet recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P3, N=737, Active, not recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Trial completion date: Jun 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> May 2024

Rampac remains a valid treatment option for patients who are unable to participate in trials or do not have access to further HER2-directed therapy beyond first line.

IGF2BP2 was found to promote the proliferation, invasion, and migration of TNBC, with no significant effect on apoptosis. By directly binding to CCL20 and c-MYC, it played a role in regulating the progression of TNBC by enhancing the methylation levels of both of these target genes.

Qualitative and quantitative MRI features offer valuable insights into low-HER2-expression breast cancer. While qualitative features are more effective for mass lesions, quantitative features are more suitable for NME lesions. These findings provide a more accessible and cost-effective approach to noninvasively identifying patients who may benefit from targeted therapy.

The nomogram could accurately predict shrinkage modes after NAT, and may help guide the individualized selection of breast conserving surgery candidates after NAT. RUVBL1-AS1 might be a promising therapeutic target of paclitaxel-based chemotherapy inHER2 + breast cancer.

Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overexpressing mCRC, offering patients an additional treatment option.

A HER2-targeted polymer drug delivery system composed of a 32-arm star polymer (SD) conjugated with the TOP1 inhibitor molecule SN-38, with a trastuzumab antigen binding fragment (HER2-Fab), has been used to target cancer cells overexpressing this receptor...The HER2-SDs demonstrated increased localization with tumor cells rather than in stromal regions, greater penetration into the tumor core and a more homogenous distribution in the tumor section than the untargeted SD. The targeted star polymer conjugated to SN-38 was tested for anti-tumor activity in a HER2-positive gastric cancer xenograft in mice and showed significantly greater efficacy compared to untargeted SDs.

This overview of the 2025 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, treatment, and follow-up of MIBC patients and is designed for effective integration into clinical practice.

This underscores the rationale for HER2-targeted therapies in these malignancies, including the use of HER2-directed tyrosine kinase inhibitors, antibody-drug conjugates, and immune-stimulating antibody conjugates. Understanding mechanisms of resistance to HER2-targeted therapies will inform possible combinatorial strategies.

Mechanistic studies unequivocally demonstrate that the primary cytotoxic species is singlet oxygen. These findings suggest that Tz-IR700 could serve as a valuable treatment option for trastuzumab-resistant HER2-positive breast cancer and may also be used as an adjuvant to fluorescence-guided surgery, improving surgical outcomes and reducing the likelihood of tumour recurrence and metastasis.

No abstract available

No abstract available

P2, N=25, Recruiting, Brown University | Trial completion date: Jan 2027 --> Sep 2027 | Trial primary completion date: Jan 2025 --> Sep 2025

The dual-mode strategy demonstrated satisfactory results in identifying breast cancer cells with varying HER2 expression levels and even in complex samples. It indicated that the electrochemical fluorescence dual-mode strategy had potential for typing and quantitative detection of cells with varying HER2 expression levels.

These carcinomas belong to the molecular apocrine carcinoma family, which includes HER2-enriched tumors driven by HER2 addiction and androgen receptor-positive luminal tumors, a subtype of triple-negative breast cancers. The latter are defined by androgen receptor pathway activation and are frequently associated with PI3K pathway alterations and cell cycle dysregulation, suggesting potential therapeutic targets.

Arm A received NACT containing docetaxel, doxorubicin, and cyclophosphamide (TAC) regimen. Arm B received NACT containing docetaxel, carboplatin, and trastuzumab (TCH) regimen...TCH exhibited greater pCR with tolerable adverse reactions in Her2neu overexpressing breast cancer compared to TAC regimen as NACT. Therefore, TCH regimen should be considered for node positive Her2neu overexpressing breast cancer.

It examines how HER2 scoring criteria for pan-tumor indications rely on immunohistochemistry (IHC) assessment, which may be prone to subjective interpretation and interobserver variability, and how these criteria differ from those used in breast, gastric, and CRC tumors. We also address the potential for NGS approaches to identify ERBB2 copy number gain (CNG) and the utility of artificial intelligence (AI) algorithms to enhance the consistency and accuracy of HER2 score interpretation for T-DXd treatment eligibility in solid tumors.

P1/2, N=34, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Notably, elevated expression of KIF11, CCNB1, and PLK1 is associated with poor prognosis in patients with TNBC. These findings contribute to an improved understanding of the epigenetic molecular mechanisms underlying TNBC progression and highlight novel biomarkers that may enhance the accuracy of TNBC diagnosis and provide potential targets for therapeutic intervention.

It is also associated with resistance against epidermal growth factor receptor (EGFR)-targeted therapies like cetuximab and panitumumab, for treatment of RAS wild-type mCRC. Furthermore, anti-HER2 therapies exhibited non-toxic profile and high efficacy in chemorefractory cases. This review delves into modern management of anti-HER2 therapies in CRC with a particular focus on recent advances and current knowledge about the prognostic and predictive value of HER2.

These findings underscore the need for personalized treatment strategies in MIBC, considering the increased risk of relapse associated with HER2 and NECTIN4 overexpression in the TC. Implementing a multi-biopsy approach is critical to enhance diagnostic accuracy.

P=N/A, N=300, Completed, Institut Curie | Trial completion date: Sep 2025 --> Mar 2025 | Trial primary completion date: Sep 2024 --> Mar 2025 | Recruiting --> Completed

Over the past decade, therapies for metastatic or advanced GEA/ESCC have expanded, with several new therapeutic targets alongside trastuzumab for metastatic HER2-positive GEA...Experts from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have formed a consensus to optimize biomarker detection and usage in clinical practice. Their recommendations aim to improve personalized treatment strategies for GEA and ESCC patients, integrating new diagnostic insights into routine care.

P2, N=128, Active, not recruiting, Baylor Breast Care Center | Trial completion date: Jan 2024 --> Jan 2026

HER2 is enriched on the surface of certain cancer cells and targeted by commercially available monoclonal antibodies, including Trastuzumab, in the treatment of breast and stomach cancers...In addition, we observed a long-lasting, over 24-h inhibition of the growth of the cancer cells after photodynamic treatment. Thus, based on these assays at the molecular and cellular levels, this study established a targeted photodynamic approach that can potentially be developed as an effective PDT for cancer treatment.

Patients with cN0 HER2-positive and triple-negative breast cancer with low-volume axillary metastases treated with upfront SLNB-alone showed excellent local control with nodal irradiation.

Such dynamic fluctuation of receptor interaction may open a window for the binding of therapeutic antibodies that are aimed at inhibiting heterodimerization, such as pertuzumab. The complementary array of state-of-the-art imaging cytometry approaches thus demonstrates a spatiotemporal pattern of spontaneous and induced receptor aggregation states that could provide mechanistic insights into the potential success of targeted therapies directed at the HER family of receptor tyrosine kinases.

A radiomics model based on US images is capable of effectively differentiating between various molecular subtypes of IBC prior to surgery, holding promise in assisting medical professionals in crafting tailored diagnostic and therapeutic strategies.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

Low-grade HER2-positive breast carcinomas constitute mostly low-stage, luminal-type, and apparently low-risk tumors, warranting investigation into whether therapy de-escalation could achieve favorable outcomes with less toxicity in this population.

The combination of inetetamab and atezolizumab impeded the growth of HER2+ EOC tumors in vivo and induced a long-term anti-tumor effect with the elevated infiltration of CD103+CD8+ cells. These findings suggest that the combination of inetetamab and atezolizumab could be a promising precision treatment strategy for HER2+ EOC patients.

HER-2/neu expression is higher in malignant cervical lesions compared to premalignant ones, suggesting its role in tumor progression. Further studies with larger sample sizes and additional variables like human papillomavirus (HPV) status are recommended to explore its prognostic potential.

P2, N=63, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> May 2025

In summary, zanidatamab has shown significant tumor response, progression-free survival, disease control, and improved quality of life in early trials, however, the lack of long-term safety and efficacy data remains a key limitation, requiring further research.

Neurological burden at BM diagnosis independently predicts survival in BC patients. Our findings emphasise incorporating the symptom status in the prognostic evaluation and reassessing BM screening in high-risk patients during prospective clinical trials.

Tucatinib, a highly selective tyrosine kinase inhibitor, demonstrated significant efficacy in combination with trastuzumab in patients with refractory mCRC, leading to its approval by the Food and Drug Administration (FDA). The future of tucatinib-based therapeutic strategies in GI malignancies depends on its integration into different treatment lines. Addressing acquired resistance using liquid biopsy-guided strategies and other TKIs like lapatinib will be paramount to improve outcomes.

The LC3β status showed no significant association with age, tumor location, tumor grade, tumor stage, nodal stage, tumor budding, tumor-infiltrating lymphocytes, MMR status, HER2 status or patient survival. Future prospective studies are recommended to further explore the utility of autophagy as a prognostic and predictive biomarker.

P1, N=554, Recruiting, Boehringer Ingelheim | Trial completion date: Jan 2028 --> Aug 2028 | Trial primary completion date: Mar 2026 --> Dec 2026