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Impacts of genomic alterations on the efficacy of HER2-targeted antibody-drug conjugates in patients with metastatic breast cancer.
J Transl Med
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, No.651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.
Background: HER2-targeted antibody-drug conjugates (ADCs) have revolutionized the treatment landscape of metastatic breast cancer. However, the efficacy of these therapies may be compromised by genomic alterations. Hence, this study aims to identify factors predicting sensitivity to HER2 ADC in metastatic breast cancer.
View Article and Find Full Text PDFERα dysfunction caused by ESR1 mutations and therapeutic pressure promotes lineage plasticity in ER breast cancer.
Nat Cancer
January 2025
Department of Discovery Oncology, Genentech, South San Francisco, CA, USA.
Multiple next-generation molecules targeting estrogen receptor α (ERα) are being investigated in breast cancer clinical trials, encompassing thousands of women globally. Development of these molecules was partly motivated by the discovery of resistance-associated mutations in ESR1 (encodes ERα). Here, we studied the impact of ERα antagonist/degraders against Esr1 mutations expressed in mouse mammary glands.
View Article and Find Full Text PDFPrimary ciliary dyskinesia (PCD, OMIM 244400) is a rare genetic disorder that affects motile cilia and is characterised by impaired mucociliary clearance of the airway epithelium, which results in chronic upper and lower airway infections. While short-read next-generation sequencing technology has been used for the genetic testing of PCD, its effectiveness is limited in identifying variants in the gene because of the nearly identical pseudogene As we confirmed that the gene was not expressed in airway cells, we obtained nasal mucosa biopsy specimens for total RNA sequencing (RNA-seq) with library enrichment using exome oligos. Among the 34 nasal samples from patients suspected of having PCD, three aberrant splicing patterns in were identified in two samples.
View Article and Find Full Text PDFOccult collision tumor of the gastroesophageal junction comprising adenocarcinomas with distinct molecular profiles.
Cancer Genet
January 2025
Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA; Rutgers Cancer Institute, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic type. Here we report such a case where comprehensive tumor profiling by next generation sequencing (NGS) as well as immunohistochemistry revealed two independent adenocarcinomas comprising what was initially diagnosed as a single adenocarcinoma of the gastroesophageal (GEJ) junction.
View Article and Find Full Text PDFImpact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.
Eur J Endocrinol
January 2025
Department of Internal Medicine IV, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).
Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.
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