LOX Inhibition Disrupts a Collagen-Integrin-MYC Axis to Suppress Progression of Invasive Lobular Carcinoma - PubMed
3 days ago
- #breast cancer
- #LOX inhibition
- #MYC axis
- Invasive lobular carcinoma (ILC) accounts for 15% of breast cancers but lacks specific therapies due to underrepresentation in clinical trials and limited preclinical models.
- A pan-lysyl-oxidase inhibitor, PXS-5505, was tested in intraductal xenograft models and found to remodel fibrillar collagen, halt tumor expansion, and prevent metastatic seeding in ER+ and triple-negative ILC models without systemic toxicity.
- CRISPR screens identified ITGAV and ITGB5 as synthetic lethal partners of CDH1, with LOX inhibition downregulating their expression along with MYC, NF-κB, and AP-1 transcriptional programs.
- Collagen fiber density/alignment and MYC/AP-1 gene signatures were used as pharmacodynamic markers for drug activity.
- The study highlights a potential ECM-integrin-MYC axis in ILC and suggests PXS-5505, alone or with endocrine therapy, for window of opportunity trials in ILC.