ArticleCancer2018
Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy.
Article in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Integrating Histological and Molecular Findings for Practical Salivary Gland Diagnostics.Head and neck pathology · 2026Review
- HER2 as a molecular trojan horse in prostate cancer: mechanistic insights and therapeutic unlocks.Molecular biology reports · 2025Review
- Epithelial‑derived head and neck squamous tumourigenesis (Review).Oncology reports · 2024Review
- Article
- Targeted molecular profiling of salivary duct carcinoma with rhabdoid features highlights parallels to other apocrine and discohesive neoplasms: which phenotype should drive classification?Head and neck pathology · 2022Article
- Article
- Sclerosing Polycystic Adenoma: Conclusive Clinical and Molecular Evidence of Its Neoplastic Nature.Head and neck pathology · 2022Article
- Whole-Genome Sequencing of Common Salivary Gland Carcinomas: Subtype-Restricted and Shared Genetic Alterations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment.Cancer cytopathology · 2020Review
- Reciprocal and Autonomous Glucocorticoid and Androgen Receptor Activation in Salivary Duct Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- A 10-year review of primary major salivary gland cancers.Ecancermedicalscience · 2020Article
- PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis.Cancers · 2019Review
- Review
- Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling.Cancer medicine · 2019Article
- The evolving landscape of salivary gland tumors.CA: a cancer journal for cliniciansReview
- PTEN Deregulation Mechanisms in Salivary Gland Carcinomas.Cancer diagnosis & prognosisReview
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundPatients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small-molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options for patients with these tumors. The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors. Currently, little is known about the role and clinical implications of alterations of the HER2/PI3K pathway in patients with SDC.
methodsThe authors investigated the clinicopathologic features, genetic alterations, and expression of key members of the HER2/PI3K pathway in 43 primary tumors and conducted in vitro functional and targeted drug-response analyses on cell lines derived from salivary epithelial carcinomas.
resultsIn primary tumors, loss of phosphatase and tensin homolog (PTEN) expression was identified in 22 of 43 tumors (51%), overexpression of HER2 was observed in 12 of 43 tumors (28%), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations were identified in 12 of 43 tumors (28%). Phosphorylated protein kinase B (p-AKT) was highly expressed in most tumors. Most tumors (70%) displayed mutually exclusive alterations of PI3K members, whereas 8 tumors (19%) had 2 or more concurrent abnormalities. In vitro studies demonstrated a direct association between PTEN loss and PI3K pathway activation and evidence of response to combined PI3Kα and PI3Kβ and/or pan-PI3K inhibitors.
conclusionsThe current analyses reveal frequent PTEN loss and mutually exclusive alterations of key PI3K pathway members in SDC and demonstrate in vitro evidence of a response to pan-PI3K inhibitors. These results provide a framework for a biomarker-based substratification of patients with SDC in future targeted therapy. Cancer 2018;124:3523-32. © 2018 American Cancer Society.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.