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|Ref Type||Journal Article|
|Authors||Rieke DT, Schröder S, Schafhausen P, Blanc E, Zuljan E, von der Emde B, Beule D, Keller U, Keilholz U, Klinghammer K|
|Title||Targeted treatment in a case series of AR+, HRAS/PIK3CA co-mutated salivary duct carcinoma.|
|Abstract Text||A subgroup of salivary duct carcinoma (SDC) harbor overexpression of the androgen receptor (AR), and co-occurring mutations in the HRAS- and PIK3CA-genes. The impact of genomic complexity on targeted treatment strategies in advanced cancer is unknown.We analyzed molecular and clinical data from an institutional molecular tumor board (MTB) to identify AR+, HRAS/PIK3CA co-mutated SDC. Follow-up was performed within the MTB registrational study or retrospective chart review after approval by the local ethics committee. Response was assessed by the investigator. A systematic literature search was performed in MEDLINE to identify additional clinically annotated cases.4 patients with AR+ HRAS/PIK3CA co-mutated SDC and clinical follow-up data were identified from the MTB. An additional 9 patients with clinical follow-up were identified from the literature. In addition to AR overexpression and HRAS and PIK3CA-alterations, PD-L1 expression and Tumor Mutational Burden > 10 Mutations per Megabase were identified as additional potentially targetable alterations. Among evaluable patients, androgen deprivation therapy (ADT) was initiated in 7 patients (1 Partial Response (PR), 2 Stable Disease (SD), 3 Progressive Disease (PD), 2 not evaluable), tipifarnib was initiated in 6 patients (1 PR, 4 SD, 1 PD). One patient each was treated with immune checkpoint inhibition (Mixed Response) and combination therapies of tipifarnib and ADT (SD) and alpelisib and ADT (PR).Available data further support comprehensive molecular profiling of SDC. Combination therapies, PI3K-inhibitors and immune therapy warrant further investigation, ideally in clinical trials. Future research should consider this rare subgroup of SDC.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|HRAS G13V PIK3CA E545K||salivary gland carcinoma||predicted - sensitive||Tipifarnib||Case Reports/Case Series||Actionable||In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response and progression-free survival lasting more than 5 months in a patient with androgen-receptor (AR)-positive salivary duct carcinoma harboring HRAS G13V and PIK3CA E545K (PMID: 37427101).||37427101|