Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

Salivary duct carcinoma (SDC) is a genetically diverse malignancy associated with several potentially targetable molecular pathways that have been uncovered by comprehensive molecular profiling. Our study detected genetic aberrations in 27 of 28 cases of SDC, including targetable alterations involving PIK3CA/PTEN, BRAF, and HER2. In addition, androgen receptor splice variant AR ‐V7 was found in approximately half of cases, which has implications in resistance to anti‐androgen therapy. AbstractSalivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized byHER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant ‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations w ere found in all but 1 case and affectedTP53 (n  = 19),HRAS (n  = 7),PIK3CA,ERBB2 (HER2), andNF1 (n  = 5 each);KMT2C (MLL3) andPTEN (n  = 3 each);BRAF (p.V600E),KDM5C andNOTCH1 (n  = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was exp...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research