In this exploratory post hoc pooled analysis, Iza-bren demonstrated promising antitumor activity and a manageable safety profile in heavily pretreated EGFR-mutated NSCLC. These findings are hypothesis-generating and are being further evaluated in ongoing randomized trials.

Our multimodal analysis establishes KIF5B as a prognostic biomarker and potential therapeutic target in BRCA, with implications for understanding immune evasion and guiding precision treatment strategies.

P2, N=30, Recruiting, Salubris Biotherapeutics Inc | Not yet recruiting --> Recruiting

Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Our work establishes the COLEC12high TAM / NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

NRG1 fusions are oncogenic drivers in non-small cell lung cancer (NSCLC), with therapeutic relevance highlighted by the FDA's designation of Zenocutuzumab for NRG1 fusion-positive cases...No significant difference in progression-free survival was seen following first-line EGFR TKI therapy between uncommon and wild-type groups. Our findings highlight the heterogeneity of NRG1 fusions in NSCLC, revealing novel fusions, unique pathway enrichments, and expression profiles that may inform future personalized treatment strategies.

Multiple therapeutic modalities have been validated, including small-molecule inhibitors (INCB7839, INCB3619, GI254023X) that suppress ligand shedding and enhance trastuzumab efficacy, RNA interference (siRNA/miRNA) for targeted gene silencing, and engineered nanocarrier drug delivery platforms that overcome therapeutic resistance. The epigenetic regulation, post-translational modifications, and diagnostic advancements, such as SERS-based serum profiling, further underscore their value as biomarkers and druggable targets. Collectively, ADAM/ADAMTS-centered interventions represent a promising direction for precision oncology and therapeutic targets for improving clinical outcomes in breast cancer.

In the context of PTEN loss and AR inhibitor resistance, Zeno did not restore sensitivity. These findings highlight the critical molecular context in which tumor microenvironment-derived NRG1 affects responsiveness to AR inhibition and suggest that targeting NRG1 is a promising strategy for overcoming resistance to androgen blockade in PTEN wild-type prostate cancers.

Our hypoxia-immune panel can accurately predict response to NAC and OS in patients with LHC and may have implications for the development of novel biomarkers and targeted therapies.

These results support the antitumor activity and safety of seribantumab in patients with advanced solid tumors harboring NRG1 fusions.

NRG1 fusions are a newly described clinically actionable target in solid tumors. We report the landscape of NRG1+ cancers and highlight the importance of RNA testing. NRG1+ PDAC is enriched in younger patients with KRAS wild-type disease and has a unique biology.

In the context of PTEN loss and AR inhibitor resistance, zenocutuzumab did not restore sensitivity. These findings highlight the critical molecular context in which tumor microenvironment (TME)-derived NRG1 impacts responsiveness to AR inhibition and suggest that targeting NRG1 is a promising strategy for overcoming resistance to androgen blockade in PTEN-wildtype prostate cancers.

P1, N=42, Not yet recruiting, Actinium Pharmaceuticals Australia Pty Limited