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Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan-Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0-47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group.
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http://dx.doi.org/10.3390/curroncol31090419 | DOI Listing |
J Clin Invest
September 2025
Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, United States of America.
Background: Localized high-risk prostate cancer (PCa) often recurs despite neoadjuvant androgen deprivation therapy (ADT). We sought to identify baseline molecular programs that predict pathologic response and reveal targetable vulnerabilities.
Methods: We profiled 147 biopsy foci from 48 MRI-visible lesions in 37 patients before 6 months of ADT plus enzalutamide and radical prostatectomy.
Life Sci
August 2025
Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka State 576104, India. Electronic address:
HER2-positive breast cancer is a distinct subtype of breast cancer defined by the overexpression of the human epithelial growth factor receptor 2 (HER2). HER2 promotes aggressive tumor growth and shows poor prognosis. HER2-targeted therapies, like trastuzumab and pertuzumab, have sufficiently improved patient outcomes, but eventually, most patients face resistance to HER2 therapies, resulting in ineffective clinical action.
View Article and Find Full Text PDFNucl Med Biol
August 2025
Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Alvin J. Siteman Cancer Center, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO 63110, USA. Electronic address:
Human Epidermal Growth Factor Receptor 2 (HER2) is a membrane receptor tyrosine kinase overexpressed in a subset of gastric cancers and is the target of multiple clinically approved therapies, including the antibody-drug conjugate trastuzumab deruxtecan (T-DXd). However, resistance to HER2-directed therapies remains a major challenge in gastric cancer. Sphingosine-1-phosphate receptor 1 (S1PR1), a G-protein-coupled receptor involved in oncogenic signaling, has been associated with poor prognosis and therapy resistance.
View Article and Find Full Text PDFInt J Mol Sci
July 2025
Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, MI, Italy.
Gastric cancer (GC) remains a major cause of cancer-related mortality worldwide, with human epidermal growth factor receptor 2 (HER2)-positive disease representing a clinically relevant subset. Trastuzumab combined with chemotherapy is the standard first-line treatment in advanced settings, following the landmark ToGA trial. However, resistance to trastuzumab has emerged as a significant limitation, prompting the need for more effective second-line therapies.
View Article and Find Full Text PDFGland Surg
July 2025
Department of Radiology, Affiliated Hospital of Qinghai University, Xining, China.
Background: Breast cancer remains the predominant contributor to global cancer-related morbidity and mortality in women. Luminal subtypes, accounting for approximately 70% of cases, demonstrate favorable prognoses through endocrine-targeted therapeutic regimens owing to hormone receptor positivity. Conversely, non-luminal breast cancer variants, including human epidermal growth factor receptor 2 (HER2)-enriched and triple-negative subtypes, exhibit aggressive biological characteristics, intrinsic endocrine therapy resistance, and require molecularly guided therapeutic strategies such as HER2-directed biologicals, platinum-based cytotoxic regimens, or radiation therapy.
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