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A glioblastoma (GBM) patient with a high tumor mutation burden (TMB-high) and mismatch repair deficiency (dMMR) exhibited a significant response to pembrolizumab, an immune checkpoint inhibitor (ICI), despite prior treatment with temozolomide (TMZ), known to induce hypermutation and potential resistance to ICIs. The rapid disease progression, indicated by 80% Ki67 positivity, was markedly countered by the positive outcome of pembrolizumab treatment. This case challenges traditional GBM treatment paradigms, demonstrating the potential of precision oncology in patients with significant TMB and dMMR, and underscores the importance of comprehensive genomic profiling in guiding clinical decisions in GBM management.
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http://dx.doi.org/10.1111/cas.16370 | DOI Listing |
Zhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Geriatric Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha 410008.
Objectives: Non-small cell lung cancer (NSCLC) is associated with poor prognosis, with 30% of patients diagnosed at an advanced stage. Mutations in the and genes are important prognostic factors for NSCLC, and targeted therapies can significantly improve survival in these patients. Although tissue biopsy remains the gold standard for detecting gene mutations, it has limitations, including invasiveness, sampling errors due to tumor heterogeneity, and poor reproducibility.
View Article and Find Full Text PDFAnal Methods
September 2025
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Avapritinib (Ayvakit™) is a highly selective inhibitor of the platelet-derived growth factor receptor alpha (PDGFRA), including D842V mutations. Avapritinib (APB) is authorized in the United States for individuals with metastatic or unresectable gastrointestinal stromal tumors (GISTs). APB is considered the exclusive therapy for adults with indolent systemic mastocytosis.
View Article and Find Full Text PDFProteomics Clin Appl
September 2025
AIBioMed Research Group, Taipei Medical University, Taipei, Taiwan.
Background: Endometrial carcinoma (EC) represents a significant clinical challenge due to its pronounced molecular heterogeneity, directly influencing prognosis and therapeutic responses. Accurate classification of molecular subtypes (CNV-high, CNV-low, MSI-H, POLE) and precise tumor mutational burden (TMB) assessment is crucial for guiding personalized therapeutic interventions. Integrating proteomics data with advanced machine learning (ML) techniques offers a promising strategy for achieving precise, clinically actionable classification and biomarker discovery in EC.
View Article and Find Full Text PDFCancer Rep (Hoboken)
September 2025
Department of Respiratory and Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Centre of Soochow University, Suzhou, Jiangsu, China.
Background: Epigenetic regulation significantly affects immune responses in lung adenocarcinoma (LUAD). However, the role of RNA N6-methyladenosine (m6A) modification, especially in obstructive sleep apnea-hypopnea syndrome (OSAHS) within LUAD, is not well understood.
Methods: This study examined m6A modification patterns in 973 LUAD patients using 23 regulatory genes.
Cancer Rep (Hoboken)
September 2025
Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.
Background: Cancer of unknown primary (CUP) is a challenging malignancy characterized by metastatic tumors with an unidentified primary site, even after extensive pathological and radiographic evaluation. Recent advancements in gene expression profiling and comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) have enabled the identification of potential tissue origins, thereby facilitating personalized treatment strategies. Although most cases of CUP present as adenocarcinomas or poorly differentiated tumors, the treatment remains largely empirical, with limited success from molecularly tailored therapies.
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