Research Birgit Van Asbroeck | Birgit Van Asbroeck

Research team

Movement Antwerp (MOVANT)

Running away from doxorubicin-induced skeletal muscle toxicity: investigating the molecular mechanisms and protective effects of physical exercise. 01/11/2022 - 31/10/2026

Abstract

Doxorubicin (DOX) is a widely used and highly effective chemotherapeutic agent with severe side effects, affecting the quality of life of cancer patients and survivors. DOX-induced skeletal muscle toxicity, especially muscle wasting and dysfunction, is of particular concern as it increases morbidity and mortality rates. In the current proposal, we aim to investigate the role of myokines and miRNAs within the mechanisms of DOX-induced skeletal muscle wasting through an in vitro (C2C12 cell line) and in vivo (mice) model. Identification of these myokines and miRNAs, that are expressed and exert their action in skeletal muscle, offer a novel theoretical basis to unravel the underlying cellular and molecular mechanisms and provide novel insights in the diagnosis and treatment of skeletal muscle wasting following DOX-treatment. We hypothesize that myokines and miRNAs play a crucial role in the pathogenesis of DOX-induced skeletal muscle wasting. In addition, we will study the potential cellular and molecular counteracting effects of muscle contraction on muscle wasting by 1) electrical pulse stimulation on DOX-treated C2C12 cells and 2) single exercise bouts in mice immediately before each DOX-cycle. We hypothesize that exercise is a feasible strategy in clinical practice to prevent DOX-induced muscle wasting. Finally, to improve clinical translatability we will also study the therapeutic use of single exercise bouts in a murine cancer cachexia model treated with DOX.

Researcher(s)

Research team(s)

Movement Antwerp (MOVANT)

Project type(s)

Research Project

Chemotherapy-induced myotoxicity requires healthy skeletal muscles 01/10/2020 - 30/09/2024

Abstract

Cancer survival has increased significantly over the last decades because of improved screening and the development of novel therapies. The downside of this positive evolution is that cancer treatment-related adverse events affecting the quality of life of cancer survivors has become an emerging concern. Physical long-term side effects of anthracycline chemotherapy, such as doxorubicin (DOX) and Cisplatin (CIS), include cardiovascular complications (heart failure), peripheral fatigue and muscle mass loss (wasting). While the cardiovascular toxicity of DOX has been extensively studied, this project aim to investigate the effects of DOX and/or CIS on skeletal muscle structure and (mitochondrial) metabolism. Additionally, we will evaluate the possible beneficial effect of physical exercise as a strategy to protect against DOX and CIS induced myotoxicity. This project aims to lay the foundation of a novel joint research line of the research groups of Movant, Cardiovascular Disease and Physiopharmacology to exploit scientific and operational synergies.