{"entity":{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","aka":["Adenoid cystic carcinoma","Mucoepidermoid carcinoma","Salivary duct carcinoma","Secretory carcinoma"],"tldr":"Salivary gland cancers are a family of over 20 rare cancers, each with its own behaviour and often its own gene fusion. Surgery and radiation treat most; drug therapy is now chosen by the specific subtype, from anti-HER2 or anti-androgen drugs to NTRK inhibitors.","summary":"Salivary gland carcinomas are defined increasingly by fusion genes: MYB-NFIB in adenoid cystic carcinoma (ACC), CRTC1-MAML2 in mucoepidermoid carcinoma, ETV6-NTRK3 in secretory carcinoma, PLAG1/HMGA2 fusions in carcinoma ex pleomorphic adenoma, and androgen receptor and HER2 in salivary duct carcinoma (SDC). Adenoid cystic carcinoma is the archetype of slow-growing disease with perineural spread and late lung metastases; salivary duct carcinoma is aggressive and resembles apocrine breast cancer.\n\nSurgery with post-operative radiotherapy (or neutron/carbon-ion therapy for unresectable ACC) is standard for localised disease; RTOG 1008 tested adding cisplatin. Systemic therapy is subtype-directed: trastuzumab-docetaxel or T-DXd for HER2-positive SDC; androgen deprivation (leuprorelin ± bicalutamide, enzalutamide) for AR-positive SDC; larotrectinib or entrectinib for ETV6-NTRK3 secretory carcinoma; lenvatinib, axitinib or rivoceranib for progressive ACC (~10-15% response, high disease control); and chemotherapy (CAP, carboplatin-paclitaxel) for others. Checkpoint inhibitors have low activity except in a minority with high TMB or PD-L1. Notch-mutant ACC (~15%, aggressive) is a target for gamma-secretase inhibitors.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Salivary_gland_tumour","links":[{"label":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"},{"label":"ESMO-EURACAN salivary gland guideline (2022)","url":"https://doi.org/10.1016/j.esmoop.2022.100602"},{"label":"Adenoid Cystic Carcinoma Research Foundation","url":"https://www.accrf.org/"}],"tags":["gap-fill","head-and-neck","rare"],"related":[],"cancers":[],"sections":[],"technologies":["imrt-igrt","carbon-ion","proton-therapy","adc","kinase-inhibitors","androgen-deprivation","cgp"],"targets":["her2","androgen-receptor","ntrk","vegf","met"],"drugs":["trastuzumab","docetaxel","trastuzumab-deruxtecan","enzalutamide","larotrectinib","entrectinib","lenvatinib","axitinib","cisplatin","carboplatin","paclitaxel","pembrolizumab"],"companies":["bayer","roche-genentech","daiichi-sankyo","eisai"],"institutions":[],"pathways":["ar-signaling","vegf-angiogenesis"],"terms":["gene-fusion","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-van-herpen-esmo-open"],"journals":[],"dependsOn":[],"notes":[],"group":"head and neck","burden":"About 1 per 100,000 per year; ~5% of head and neck cancers; more than 20 histologic types, most individually very rare.","subtypes":["Adenoid cystic carcinoma (MYB-NFIB; NOTCH1-mutant subset)","Mucoepidermoid carcinoma (CRTC1/3-MAML2)","Salivary duct carcinoma (AR+, HER2+ in ~30%)","Secretory carcinoma (ETV6-NTRK3)","Acinic cell carcinoma (NR4A3)","Carcinoma ex pleomorphic adenoma","Polymorphous adenocarcinoma, myoepithelial and others"],"biomarkers":["Histotype with fusion confirmation (MYB, MAML2, ETV6-NTRK3, NR4A3)","HER2 IHC/ISH and androgen receptor IHC (salivary duct carcinoma)","NTRK fusion (secretory carcinoma)","NOTCH1 mutation (adenoid cystic, shorter survival)","Perineural invasion, grade, margin status","PD-L1 / TMB (rarely high)"],"standardOfCare":[{"setting":"Localised, resectable","approach":"Complete resection (parotidectomy with facial-nerve preservation where possible) and neck dissection for high-grade; post-operative radiotherapy for high-grade, close margins, perineural invasion, T3-4 or node-positive disease.","refs":["imrt-igrt","proton-therapy"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck (Salivary)","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Unresectable localised","approach":"Definitive radiotherapy; carbon-ion or neutron therapy for adenoid cystic carcinoma where available (COSMIC, Heidelberg).","refs":["carbon-ion","imrt-igrt"],"guideline":{"version":"ESMO salivary gland guideline 2022"}},{"setting":"Recurrent/metastatic, subtype-directed","approach":"HER2+ SDC: trastuzumab + docetaxel or trastuzumab deruxtecan; AR+ SDC: androgen deprivation (leuprorelin/bicalutamide; enzalutamide); NTRK-fused secretory carcinoma: larotrectinib or entrectinib; ACC: lenvatinib or axitinib for progressive disease, observation if indolent.","refs":["trastuzumab","docetaxel","trastuzumab-deruxtecan","enzalutamide","larotrectinib","entrectinib","lenvatinib","axitinib"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck (Salivary)"}},{"setting":"Recurrent/metastatic, other","approach":"Platinum-based chemotherapy (CAP, carboplatin-paclitaxel); pembrolizumab for TMB-H/MSI-H or PD-L1-positive; clinical trials.","refs":["cisplatin","doxorubicin","cyclophosphamide","carboplatin","paclitaxel","pembrolizumab"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck (Salivary)"}}],"stateOfArt":["Salivary gland cancer is where fusion-defined pathology has most changed practice: ETV6-NTRK3 secretory carcinoma responds to NTRK inhibitors in ~90%.","Salivary duct carcinoma is treated like a HER2+/AR+ breast cancer, with T-DXd giving durable responses.","VEGFR inhibitors stabilise adenoid cystic carcinoma but rarely shrink it; NOTCH inhibition targets its worst subset.","Carbon-ion therapy for unresectable ACC is an example of particle therapy with a clear niche."],"history":[{"year":1859,"title":"Billroth describes 'cylindroma' (adenoid cystic carcinoma)","refs":[]},{"year":1994,"title":"Neutron therapy trial (RTOG-MRC) in unresectable salivary cancer","refs":[]},{"year":2003,"title":"CRTC1-MAML2 fusion in mucoepidermoid carcinoma (Tonon)","refs":["gene-fusion"]},{"year":2009,"title":"MYB-NFIB fusion in adenoid cystic carcinoma (Persson, PNAS)","refs":[]},{"year":2010,"title":"Mammary analogue secretory carcinoma with ETV6-NTRK3 described (Skálová)","refs":["ntrk"]},{"year":2018,"title":"Larotrectinib approved tumour-agnostically, including secretory carcinoma","refs":["larotrectinib"]},{"year":2019,"title":"Trastuzumab-docetaxel in HER2+ salivary duct carcinoma (Takahashi, JCO); lenvatinib in ACC (Tchekmedyian, JCO)","refs":["trastuzumab","docetaxel","lenvatinib"]},{"year":2022,"title":"ESMO-EURACAN salivary gland guideline","refs":[]}],"pipeline":["trastuzumab-deruxtecan","lenvatinib","larotrectinib","carbon-ion","gotistobart","rem-422"],"openProblems":["Adenoid cystic carcinoma: no drug induces meaningful shrinkage; 20-year survival remains poor.","Trials are tiny; most evidence is phase 2 or retrospective.","Facial nerve sacrifice and disfigurement in surgery.","Immunotherapy largely inactive."]},"route":"/cancers/salivary-gland/","neighbours":{"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"carbon-ion","kind":"technology","name":"Carbon-ion therapy","route":"/technologies/carbon-ion/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"crtc1","kind":"target","name":"CRTC1","route":"/targets/crtc1/"},{"id":"esrra","kind":"target","name":"ESRRA","route":"/targets/esrra/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"notch1","kind":"target","name":"NOTCH1","route":"/targets/notch1/"},{"id":"notch2","kind":"target","name":"NOTCH2","route":"/targets/notch2/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"ppp2r1a","kind":"target","name":"PPP2R1A","route":"/targets/ppp2r1a/"},{"id":"runx1","kind":"target","name":"RUNX1","route":"/targets/runx1/"},{"id":"smarca2","kind":"target","name":"SMARCA2","route":"/targets/smarca2/"},{"id":"spen","kind":"target","name":"SPEN","route":"/targets/spen/"},{"id":"trrap","kind":"target","name":"TRRAP","route":"/targets/trrap/"},{"id":"tyw2","kind":"target","name":"TYW2","route":"/targets/tyw2/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"}],"drug":[{"id":"axitinib","kind":"drug","name":"Axitinib","route":"/drugs/axitinib/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"gotistobart","kind":"drug","name":"Gotistobart","route":"/drugs/gotistobart/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"rem-422","kind":"drug","name":"REM-422","route":"/drugs/rem-422/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"company":[{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"daiichi-sankyo","kind":"company","name":"Daiichi Sankyo","route":"/companies/daiichi-sankyo/"},{"id":"eisai","kind":"company","name":"Eisai","route":"/companies/eisai/"},{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"vegf-angiogenesis","kind":"pathway","name":"VEGF angiogenesis","route":"/pathways/vegf-angiogenesis/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"paper":[{"id":"paper-van-herpen-esmo-open","kind":"paper","name":"Salivary gland cancer: ESMO-European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up","route":"/key-papers/paper-van-herpen-esmo-open/"}],"biomarker":[{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"}],"journal":[{"id":"head-and-neck-pathology","kind":"journal","name":"Head and neck pathology","route":"/journals/head-and-neck-pathology/"}],"cancer":[{"id":"acinic-cell-carcinoma-salivary","kind":"cancer","name":"Acinic cell carcinoma of the salivary glands","route":"/cancers/acinic-cell-carcinoma-salivary/"},{"id":"adenoid-cystic-carcinoma","kind":"cancer","name":"Adenoid cystic carcinoma","route":"/cancers/adenoid-cystic-carcinoma/"},{"id":"carcinoma-ex-pleomorphic-adenoma","kind":"cancer","name":"Carcinoma ex pleomorphic adenoma","route":"/cancers/carcinoma-ex-pleomorphic-adenoma/"},{"id":"mucoepidermoid-carcinoma","kind":"cancer","name":"Mucoepidermoid carcinoma","route":"/cancers/mucoepidermoid-carcinoma/"},{"id":"salivary-duct-carcinoma","kind":"cancer","name":"Salivary duct carcinoma","route":"/cancers/salivary-duct-carcinoma/"}],"trial":[{"id":"nct04325828","kind":"trial","name":"A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma","route":"/trials/nct04325828/"},{"id":"nct05377996","kind":"trial","name":"A Study of Emiltatug Ledadotin (Emi-Le) in Participants With Solid Tumors","route":"/trials/nct05377996/"},{"id":"nct06781567","kind":"trial","name":"Clinical Trial of HG146 Administered to Participants with Adenoid Cystic Carcinoma","route":"/trials/nct06781567/"},{"id":"nct06118086","kind":"trial","name":"Study of REM-422 in Patients With Recurrent, Metastatic, or Unresectable Adenoid Cystic Carcinoma","route":"/trials/nct06118086/"},{"id":"nct03556228","kind":"trial","name":"VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma","route":"/trials/nct03556228/"}]}}