What Is This Summary About?: This plain language summary reports the findings of a case series, a study which evaluated a small number of people who had a certain type of cancer. This case series looked at how well a drug called afatinib worked in people who have a rare type of cancer called neuregulin-1 (also called ) gene fusion-positive cancer. Six people with gene fusion-positive cancer were treated with afatinib, including five with lung cancer and one with gastrointestinal cancer. After treatment, people were monitored regularly to see if their tumors had grown (known as tumor progression).
What Were The Results?: After being treated with afatinib for up to 16 months, two people had stable disease (meaning their cancer did not get worse or improve). Three people had a partial response (meaning they showed a decrease in the size of their tumor) for over 18 months. One person had a partial response after being treated with afatinib for 11 months.
What Do The Results Mean?: Afatinib showed encouraging results which suggest it may be a potential treatment for fusion-driven cancers, as it delayed tumor progression and decreased tumor size for some people with gene fusion-positive tumors. These case reports warrant the conduct of a clinical trial including a larger number of people to definitively confirm how well afatinib works in treating people with gene fusion-positive cancers.
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http://dx.doi.org/10.2217/fon-2021-0855 | DOI Listing |
Endocr Relat Cancer
January 2025
A Nikitski, Department of Pathology, University of Pittsburgh, Pittsburgh, 15261, United States.
Approximately 10-20% of thyroid cancers are driven by gene fusions, which activate oncogenic signaling through aberrant overexpression, ligand-independent dimerization, or loss of inhibitory motifs. We identified 13 thyroid tumors with thyroglobulin (TG) gene fusions and aimed to assess their histopathology and the fusions' oncogenic and tumorigenic properties. Of 11 cases with surgical pathology, 82% were carcinomas and 18% noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP).
View Article and Find Full Text PDFWorld J Clin Cases
January 2025
Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu 42601, South Korea.
Background: The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics, increasingly supported by molecular genetic diagnostics. Data on neurotrophic tyrosine receptor kinase () gene fusion-positive uterine sarcoma, potentially aggressive and morphologically similar to fibrosarcoma, are limited due to its recent recognition. Pan-TRK immunohistochemistry (IHC) analysis serves as an effective screening tool with high sensitivity and specificity for -fusion malignancies.
View Article and Find Full Text PDFJ Pathol
January 2025
Laboratory of Pathology, Center for Cancer Research, NCI, Bethesda, MD, USA.
Rhabdomyosarcoma (RMS) is a family of phenotypically myogenic paediatric cancers consisting of two major subtypes: fusion-positive (FP) RMS, most commonly involving the PAX3::FOXO1 fusion gene, formed by the fusion of paired box 3 (PAX3) and forkhead box O1 (FOXO1) genes, and fusion-negative (FN) RMS, lacking these gene fusions. In humans, DNA methylation patterns distinguish these two subtypes as well as mutation-associated subsets within these subtypes. To investigate the biological factors responsible for these methylation differences, we profiled DNA methylation in RMS tumours derived from genetically engineered mouse models (GEMMs) in which various driver mutations were introduced into different myogenic lineages.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Division of General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Hepatoblastoma (HBL) and fibrolamellar hepatocellular carcinoma (FLC) are the most common liver malignancies in children and young adults. FLC oncogenesis is associated with the generation of the fusion kinase, DNAJB1-PKAc (J-PKAc). J-PKAc has been found in 90% of FLC patients' tumors but not in other liver cancers.
View Article and Find Full Text PDFCancer Med
January 2025
Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Background: The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established.
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