Izalontamab brengitecan (Iza-bren; BL-B01D1) is a bispecific ADC targeting EGFR and HER3 that has demonstrated activity in other malignancies. Importantly, tumor tissue obtained at progression after BL-B01D1 treatment confirmed ABCG2 upregulation, validating a clinically relevant resistance mechanism. These findings support BL-B01D1 as a promising therapeutic strategy in mCRPC and nominate ABCG2 as a rational target for overcoming resistance.

Drug sensitivity analysis revealed that Sapitinib was more effective in the high-risk group (HRG), while Doramapimod was more effective in the low-risk group (LRG) (P < 0.0001)...Finally, genes in the clinical samples also showed the same expression trend. In the present investigation, two prognostic genes were identified, and subsequently, a predictive risk model was established, which may serve as a valuable reference for the clinical management of PDAC.

iza-bren demonstrated encouraging antitumor activity and a manageable safety profile in pretreated NSCLC patients with diverse GAs outside of classical EGFR mutations, especially in EGFR exon20ins/nonclassical and HER2 mutations.

Collectively, our work links GARG expression to CRC prognosis and immune features, and functionally implicates GDI1 in tumor cell aggressiveness, supporting its further study as a potential therapeutic target.

P1, N=18, Not yet recruiting, M.D. Anderson Cancer Center

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.