State of the art and future directions in the treatment of metastatic adenoid cystic carcinoma

Purpose of review Metastatic adenoid cystic carcinoma (ACC) remains a therapeutic challenge with no approved systemic standard of care. This review highlights recent advances in ACC biology and emerging therapeutic strategies that may improve outcomes for patients with advanced disease. Recent findings Recent progress in understanding the molecular biology of ACC has led to the investigation of novel systemic therapies. Recent studies have focused on targeted agents and immuno-oncology approaches. VEGFR-targeting tyrosine kinase inhibitors, such as lenvatinib and axitinib, have shown encouraging disease control rates and are now considered standard options. Immunotherapy has demonstrated limited efficacy. New agents targeting oncogenic drivers, such as NOTCH1 mutations and epigenetic regulators like PRMT5, have demonstrated preliminary activity in early-phase clinical trials. Additional strategies, including B7-H4 targeted antibody-drug conjugates, MYB-directed vaccines and degraders, and MDM2 inhibitors for TP53 wild-type tumors, offer strong biological rationale for further development. Summary While conventional chemotherapy and immune checkpoint inhibitors remain largely ineffective, advances in ACC biology have driven the development of mechanism-based treatments. Future trials should prioritize biomarker-guided patient selection, rational combinations, and integration of molecular diagnostics to improve outcomes in this indolent but ultimately fatal disease.