학술논문

Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment.
Document Type
Article
Source
Cancers. Mar2024, Vol. 16 Issue 5, p1075. 13p.
Subject
*CACHEXIA treatment
*BIOPSY
*LEUCOCYTES
*SKELETAL muscle
*EXERCISE
*ANIMALS
*RATS
*EXPERIMENTAL design
*CELL culture
*ANIMAL experimentation
*RESEARCH methodology
*TUMORS
*CACHEXIA
*MUSCULAR atrophy
*BIOMARKERS
*DISEASE progression
*DISEASE complications
Language
ISSN
2072-6694
Abstract
Simple Summary: Currently, muscle testing remains underutilized in cancer cachexia research, since muscle biopsies are mainly performed at the end of experimental protocols. We aimed to introduce the concept of longitudinal muscle testing for cancer cachexia by initially demonstrating its feasibility and safety for the test subjects. Following that, we tested the hypothesis on a tumor-bearing rat model. Results were indicative of heterogeneity in cancer cachexia manifestation between different subjects and throughout the disease course. There is an abundance of researched pathways and mechanisms of cachexia, as well as interventions to target them. Thus, moving forward, developing biomarkers to suggest "what to target and when to do it" is essential. Sequential muscle biopsies can serve as a promising tool to guide personalized precision treatment for cancer cachexia, as well as to monitor the disease evolution and response to therapy. In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research. [ABSTRACT FROM AUTHOR]