HER-2 mutation

These results demonstrate that both dPCR and NGS-based liquid biopsy workflows can be successfully implemented for ESR1 mutation testing in routine clinical practice using locally validated assays. This multicentre verification study provides practical guidance on assay verification, DNA input requirements, and key analytical parameters required to ensure reliable ESR1 mutation detection across different European laboratories. Robust analytical verification of ESR1 testing may improve diagnostic reliability and support personalized treatment strategies for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

Due to limited germline and epigenetic data, MSI-H tumors could not be classified as Lynch-associated or sporadic. Overall, MSI-H and MSS CRCs in the Chinese population demonstrate distinct molecular landscapes in terms of TMB, HRD, EBV status, and driver gene alterations, underscoring the molecular heterogeneity of MSI-H CRC and the need for future studies integrating germline and epigenetic data to refine subtype classification.

The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant's pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact.

P2, N=60, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

Concerning treatment, in advanced HER2-positive, Non-Squamous NSCLC tumors, the first-line treatment is Platinum-based + Pemetrexed chemotherapy, with or without immunotherapy, because no HER2-targeted antibody therapy has yet been approved for initial treatment. After progression, HER2-targeted antibody-drug conjugates like Trastuzumab-Deruxtecan and Ado Trastuzumab-Emtansine may offer patients clinical benefits. New HER2-selective tyrosine kinase inhibitors, such as zongertinib and sevabertinib, have shown promising results, including patients previously treated with antibody-drug conjugates (ADCs). Recent advances, including next-generation ADCs such as SHR-A1811 and A166, and bispecific antibodies, such as zenocutuzumab for NRG1 fusion-positive disease, which are also expanding treatment options. Overall, advances in diagnostics and new targeted therapies are changing how HER2-altered NSCLC is treated and are helping to make care more personalized.

The LiBRA study supports liquid biopsy as a prognostic and monitoring tool in BRAF V600E-mutated NSCLC undergoing targeted therapy.

P1, N=108, Recruiting, Daiichi Sankyo | Active, not recruiting --> Recruiting

P1/2, N=400, Recruiting, Bayer | Trial completion date: Dec 2026 --> Jun 2029 | Active, not recruiting --> Recruiting

P2, N=152, Not yet recruiting, The Third Xiangya Hospital of Central South University

PROTACs, especially ER degraders, suggest a potential strategy for addressing endocrine resistance in advanced ER + breast cancer, as reflected in encouraging preliminary clinical data. This integrated analysis highlights the rapid translation of this technology while underscoring the critical need to expand target scope, address inherent resistance mechanisms, and broaden applications to other breast cancer subtypes. Our article synthesizes current knowledge and trial landscape, thereby providing a consolidated foundation to inform future research and clinical development of PROTACs in breast cancer.

MTT was the most common second-line treatment, however, outcomes were generally poor, emphasizing the unmet need for effective second-line treatments for HER2-mutant NSCLC.

DS-8201 demonstrates potential as one of the effective salvage therapies following RC48 failure in HER2 altered solid tumors, showing significantly better disease control and a distinct, manageable toxicity profile. These findings highlight the importance of selecting personalized ADCs based on molecular subtypes and toxicity factors and provide a basis for future, larger-scale prospective studies.