NRG1 fusion

Finally, JK07 exhibited therapeutic potential in heart failure in rhesus macaques. In conclusion, this work demonstrates selective HER4 activation is sufficient for NRG-1 to improve myocardial function in multiple pre-clinical heart failure models and that JK07 holds promise as a potential therapeutic intervention for heart failure.

Zenocutuzumab demonstrated clinically meaningful and durable antitumor activity with a favorable safety profile in patients with advanced NRG1+ cholangiocarcinoma.

This observation highlights the potential clinical benefit of repeating NGS even in late stages of breast cancer treatment. Furthermore, NGS may expand our ability to utilize targeted agents in not only early phase but also later phase breast cancer treatment.

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.

Our results support the incorporation of ALK immunohistochemistry as a screening tool and demonstrate the utility of anchored multiplex PCR-based RNA sequencing for the detection of therapeutically relevant fusions, particularly those with uncommon partners. This integrated approach may refine the diagnosis and support consideration of ALK-directed therapy in these rare tumors.

P4, N=535, Recruiting, Peking Union Medical College Hospital; Peking Union Medical College Hospital

This gives a better understanding of the biology of NRG1 fusions, and will help in the development of new therapeutic approaches. Our methodology described in this review can also be used for the study of other genes with disease-related fusions.

KRAS G12C-mutated NSCLC is clinically aggressive and frequently shows solid growth with rhabdoid, plasmacytoid, or SCC-like morphology, which may lead to misclassification and missed genetic testing. Immunohistochemistry and molecular profiling are essential for accurate classification and enabling targeted therapy.

These disruptions could impair tumour-suppressive pathways, presenting additional therapeutic targets. This research emphasises the broader relevance of fusion-driven mechanisms in cPAC tumorigenesis, advancing the understanding of both canine and human lung cancers for clinical and comparative studies.

Emerging immunotherapies targeting Claudin18.2 and CXCR4 offer hope to overcome tumor resistance. Together, these strategies underscore the promise of molecular stratification, synthetic lethality, and novel targets to improve pancreatic cancer survival.

Multiple strategies are employed to achieve ever-increasing efficacy of the newly proposed therapies, including combination therapies with other targeted approaches, small compounds, and monoclonal antibodies. This narrative review summarizes the available data on the spectrum of all available drugs targeting NRG1/HER deregulation in cancers with NRG1 fusions, their chemistry, pharmacodynamics, pharmacokinetics, and metabolism, as well as the clinical efficacy in NRG1-positive patients.