A view on drug resistance in cancer
Recent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein.
Background: Adenoid cystic carcinoma (ACC) is a rare tumor of secretory glands, most commonly arising from the salivary glands, with a slow growth kinetics and a propensity for perineural invasion. Recent molecular characterisation has identified a recurrent MYB:NFIB gene fusion on chromosome 6:9 and additional frequent mutations, many of which may be therapeutically actionable. Methods: A comprehensive search of PubMed and conference abstracts evaluated genetic and therapeutic advances in ACC. Results: The MYB:NFIB fusion underlies overexpression of the MYB oncoprotein; other frequently altered genes include c‑KIT, FGFR1, EGFR, HER2, SOX4, casein kinase 1ε, and frizzled‑7. Representative trials of targeted agents (e.g., the tyrosine‑kinase inhibitor dovitinib) have demonstrated tumor‑growth inhibition, but objective responses remain rare. Tumor sequencing data also reveal pathway alterations in Wnt/β‑catenin, Notch, and PI3K signalling. Conclusion: ACC’s characteristic chromosomal translocation and additional mutations provide a rationale for targeted therapies, yet the rarity and indolent nature of the disease limit clinical trial accrual. Ongoing studies are testing inhibitors of FGF‑R signalling and other pathways; novel approaches based on whole‑tumor genome sequencing are in development.
The low response rates to conventional therapies and the uncommon yet aggressive nature of ACC underline the need for new targeted treatments. Understanding the genetic drivers of ACC is essential for rational drug design and for improving outcomes for patients with this rare malignancy.
Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.
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