{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:39:27Z","timestamp":1784302767522,"version":"3.55.0"},"reference-count":158,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,20]],"date-time":"2022-11-20T00:00:00Z","timestamp":1668902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent\/metastatic (R\/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R\/M ACC. We review the evidence for the most widely used systemic agents \u2014 cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR \u2014 in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R\/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R\/M ACC.<\/jats:p>","DOI":"10.3390\/cancers14225698","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T04:13:36Z","timestamp":1669004016000},"page":"5698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Approaches to the Management of Metastatic Adenoid Cystic Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-9975","authenticated-orcid":false,"given":"Rex H.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine C.","family":"Wai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Stanford University, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick K.","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-8202","authenticated-orcid":false,"given":"Hyunseok","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.oraloncology.2015.04.005","article-title":"Adenoid Cystic Carcinoma of the Head and Neck\u2014An Update","volume":"51","author":"Rodrigo","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1002\/cncr.32208","article-title":"Minor Salivary Gland Tumors of the Head and Neck-Memorial Sloan Kettering Experience: Incidence and Outcomes by Site and Histological Type","volume":"125","author":"Hay","year":"2019","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.oraloncology.2007.05.010","article-title":"The Range and Demographics of Salivary Gland Tumours Diagnosed in a UK Population","volume":"44","author":"Jones","year":"2008","journal-title":"Oral Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.oraloncology.2006.06.005","article-title":"Adenoid Cystic Carcinoma of the Buccal Vestibule: A Case Report and Review of the Literature","volume":"42","author":"Giannini","year":"2006","journal-title":"Oral Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1002\/cncr.27408","article-title":"Adenoid Cystic Carcinoma of the Head and Neck: Incidence and Survival Trends Based on 1973-2007 Surveillance, Epidemiology, and End Results Data","volume":"118","author":"Ellington","year":"2012","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1245\/s10434-014-4106-7","article-title":"Elective Neck Dissection in Patients with Head and Neck Adenoid Cystic Carcinoma: An International Collaborative Study","volume":"22","author":"Amit","year":"2015","journal-title":"Ann. 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