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Chemotherapy-induced cognitive impairments (CICI), colloquially known as "chemobrain," represents a profound and debilitating side effect experienced by a significant number of cancer survivors, impacting their memory, multitasking, and quality of life. This review critically evaluates the molecular mechanisms underlying CICI, with a particular focus on the insights gained from transcriptomic analyses. As cancer incidence rises globally, understanding the complex interplay between chemotherapy agents and their cognitive repercussions becomes increasingly vital. Key mechanisms implicated in CICI include blood-brain barrier disruption, neuroinflammation, and oxidative stress as a result of various chemotherapy treatments, such as doxorubicin, cisplatin, and paclitaxel. We delve into advanced transcriptomic methodologies including RNA sequencing, cDNA microarrays, and single-cell transcriptomics that elucidate the alteration in gene expression profiles associated with CICI and provide a deeper understanding of the underlying pathophysiological processes. Furthermore, we emphasize the importance of developing comprehensive single-cell atlases and employing spatial transcriptomics to uncover cellular heterogeneity and the spatial dynamics of gene expression across different brain regions. This review consolidates the existing literature on the transcriptomic profile of CICI, highlighting potential genes and pathways while suggesting future research avenues aimed at mitigating cognitive dysfunction. Ultimately, integrating transcriptomic findings with clinical insights is essential for the development of targeted, personalized interventions, thereby improving cognitive health and overall quality of life for cancer survivors dealing with long-term impacts of their treatment.
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http://dx.doi.org/10.1186/s40478-025-02102-z | DOI Listing |
JNCI Cancer Spectr
September 2025
Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States.
Background: Cancer survivors may be more likely to experience accelerated declines in physical function compared to cancer-free controls, but objective data and knowledge of preventive interventions are limited.
Methods: The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, single-blinded, randomized trial conducted at 8 centers across the United States that enrolled 1635 sedentary adults aged 70-89 years and with physical limitations but who could walk 400 m at baseline, of which 371 (22.7%) reported a history of cancer.
Neurotoxicology
September 2025
Reynosa-AztlanUnidad Académica Multidisciplinaria Reynosa-Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, Mexico. Electronic address:
Cisplatin-induced peripheral neuropathy (CIPN) is one of the most prevalent long-term complications in pediatric cancer survivors reaching adulthood. However, very few studies have evaluated the long-term effects of cisplatin administered to the young population on the peripheral nervous system and assessed whether these effects are sex-dependent. Thus, we aimed to assess baseline mechanical withdrawal thresholds (a CIPN measurement), the density of CGRP and PGP9.
View Article and Find Full Text PDFSupport Care Cancer
September 2025
Carbone Cancer Center, School of Medicine and Public Health, University of WI-Madison, Madison, WI, USA.
Purpose: For cancer survivors, self-efficacy is needed to manage the disease and the effects of treatment. The COVID-19 pandemic disrupted cancer-related healthcare, which may have impacted self-management self-efficacy. We investigated self-efficacy reported by cancer survivors during COVID-19, including associations with healthcare disruptions, distress, and general health.
View Article and Find Full Text PDFInt J Surg
September 2025
State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Introduction: Recent advancements in surgical techniques and perioperative care have improved cancer survival rates, yet postoperative comorbidity and mortality remain a critical concern. Despite progress in cancer control, systematic analyses of long-term mortality trends and competing risks in surgery-intervened cancer populations are lacking. This study aimed to quantify temporal patterns of postoperative mortality causes across 21 solid cancers and identify dominant non-cancer risk factors to inform survivorship care strategies.
View Article and Find Full Text PDFHead Neck
September 2025
Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.
Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed.