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#小分子/降解剂

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Oct 8Thu
  1. N Engl J Med40

    Advances in Systemic Treatment of Breast Cancer.

    A New England Journal of Medicine review traces systemic therapy for breast cancer since 2020, covering targeted therapies, antibody-drug conjugates and immunotherapy across biologic subtypes. CDK4/6 inhibitors remain foundational in hormone-receptor-positive, HER2-negative disease, trastuzumab deruxtecan is reshaping HER2-positive treatment, and immune checkpoint inhibitors have improved outcomes in triple-negative breast cancer. Unresolved issues include treatment sequencing, predictive biomarkers, circulating tumor DNA analysis and equitable access to high-cost therapies.

  2. nature.com66

    Molecular glue targets ALK resistance

    Conery et al. report in Nature the discovery and preclinical characterization of TRI-611, a selective, brain-penetrant molecular glue degrader that targets ALK fusion proteins in non-small-cell lung cancer, including tyrosine kinase inhibitor-resistant variants. The approach aims to address acquired resistance driven by ALK kinase domain mutations, TKI toxicity, and limited CNS penetration that hinders treatment of brain metastases. Further preclinical and clinical development would follow.

    Why it matters: Molecular glue degrader offers a new way to overcome ALK TKI resistance and CNS penetration limits in NSCLC.

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