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Purpose: Tumor suppressor p53 (TP53) mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials And Methods: We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: group 1, alpelisib; group 2, poziotinib; group 3, nintedanib; and group 4, abemaciclib. If there was no identifiable target, the patients were allocated to group 5 (durvalumab±tremelimumab).
Results: TP53 mutations were detected in 116/179 patients (64.8%), more frequently in human papillomavirus-negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion: TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.
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http://dx.doi.org/10.4143/crt.2024.836 | DOI Listing |
J Cancer Res Clin Oncol
September 2025
Division of Gastroenterology, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
Purpose: Next-generation sequencing (NGS) has revolutionized cancer treatment by enabling comprehensive cancer genomic profiling (CGP) to guide genotype-directed therapies. While several prospective trials have demonstrated varying outcomes with CGP in patients with advanced solid tumors, its clinical utility in colorectal cancer (CRC) remains to be evaluated.
Methods: We conducted a prospective observational study of CGP in our hospital between September 2019 and March 2024.
Urol Oncol
September 2025
Nutritional, Genes and Human Disease Laboratory, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh. Electronic address:
Background: Understanding the mutational landscape is critical for elucidating the molecular mechanisms driving cancer progression. This study aimed to profile somatic mutations in bladder cancer patients (N=7) from Bangladesh to provide insights into the genetic alterations underlying this malignancy.
Methods: We performed targeted sequencing of 50 oncogenes and tumor suppressor genes using the Ion AmpliSeq Cancer Hotspot Panel v2 on tumor and matched blood samples from seven bladder cancer patients.
J Immunother Cancer
September 2025
Affini-T Therapeutics Inc, Watertown, Massachusetts, USA.
T-cell receptors (TCRs) recognize antigens derived from fragments of somatically expressed proteins that are degraded by the proteasome and presented by specific human leukocyte antigen (HLA) molecules. Recent therapeutic advances using the TCR as a tumor-targeting moiety have focused attention on loss of heterozygosity (LOH) as a potential resistance mechanism. Allele-specific LOH, rather than allele-agnostic, is particularly pertinent, but rarely evaluated.
View Article and Find Full Text PDFAnnu Rev Pathol
September 2025
3Department of Pathology, Stanford University, Stanford, California, USA;
Clonal hematopoiesis, originally identified as a precursor to hematologic malignancies, has emerged as a significant factor in various nonmalignant diseases. Recent research highlights how somatic mutations in hematopoietic stem cells lead to the expansion of circulating mutated immune cells that exert profound effects on organ function and disease progression. These mutated clones display altered inflammatory profiles and tissue-specific functional consequences, contributing to various diseases including atherosclerotic cardiovascular disease, osteoporosis, heart failure, and neurodegenerative conditions.
View Article and Find Full Text PDFPLoS Comput Biol
September 2025
Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America.
Fanconi Anemia (FA) is a heritable syndrome characterized by DNA damage repair deficits, frequent malformations and a significantly elevated risk of bone marrow failure, leukemia, and mucosal head and neck squamous cell carcinomas (HNSCC). Hematopoietic stem cell gene therapy can prevent marrow failure and lower leukemia risk, but mucosal gene therapy to lower HNSCC risk remains untested. Major knowledge gaps include an incomplete understanding of how rapidly gene-corrected cellular lineages could spread through the oral epithelium, and which delivery parameters are critical for ensuring efficient gene correction.
View Article and Find Full Text PDF