2. Academic Validation
  3. A Comprehensive Adenoid Cystic Carcinoma-Derived Organoid Platform for Disease Modeling and Drug Screening Captures Interpatient Heterogeneity

A Comprehensive Adenoid Cystic Carcinoma-Derived Organoid Platform for Disease Modeling and Drug Screening Captures Interpatient Heterogeneity

  • Cells. 2026 Feb 23;15(4):383. doi: 10.3390/cells15040383.
Yingyue Chai 1 2 3 4,  Yi Sui 1 2 3 4,  Xinyuan Zhang 1 2 3 4,  Shang Xie 1 2 3 4,  Yifan Kang 1 2 3 4,  Yanrui Feng 2 3 4 5,  Xiaofeng Shan 1 2 3 4,  Zhigang Cai 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery and Oral Emergency, Peking University School and Hospital of Stomatology, Beijing 100081, China.
  • 2 National Center for Stomatology, Beijing 100081, China.
  • 3 National Clinical Research Center for Oral Diseases, Beijing 100081, China.
  • 4 National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.
  • 5 Department of Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China.
PMID: 41744826 DOI: 10.3390/cells15040383
Abstract

Salivary adenoid cystic carcinoma (ACC) is a highly aggressive salivary gland malignancy characterized by infiltrative growth patterns that hinder complete resection. Lacking effective chemotherapy, recurrent or metastatic ACC remains clinically incurable. This research aimed to develop an efficient culture system for ACC organoids, which can preserve tumor heterogeneity and establish a reliable drug screening platform. Under our optimized culture conditions, ACC organoids grew rapidly and successfully recapitulated three characteristic histopathological patterns. Whole-genome Sequencing (WGS) further confirmed they mirrored the genomic features of their parental tumors, including significantly mutated genes, non-coding regulatory region mutations, copy number variation, and minor allele frequency. RNA Sequencing confirmed that ACC organoids recapitulated the MYB-NFIB fusion gene. At the protein level, these organoids contained multiple cellular components, including epithelial cells, mesenchymal cells, K7+ duct cells, a-SMA+ myoepithelial cells, K5+ basement membrane cells, and CD44+ tumor stem cells, with proper spatial distribution patterns. With an 88% success rate, the first ACC Organoid platform, incorporating normal salivary gland (SG) organoids as toxicity controls, enabled high-throughput drug testing within two weeks. In conclusion, we developed an efficient culture system for ACC organoids that can preserve tumor heterogeneity and establish a reliable drug screening platform for mechanistic studies and personalized precision therapy research.

Keywords

ACC; drug screening; organoids; personalized medicine; tumor model.

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