Measuring the oncological value of exercise and statins (MOVES): Changing the tumour microenvironment with exercise and statins — an exploratory pilot trial

Background Hypoxia is a critical mechanism by which cancer cells evade the immune response, promoting tumour survival and progression. Many cancer types exhibit upregulated lipid and cholesterol metabolism as a fundamental adaptation strategy to the hypoxic tumour microenvironment. This metabolic shift supports cancer cell survival under oxygen-deprived conditions, enhancing their ability to resist treatment and metastasize. We will explore whether exercise reduces tumour hypoxia via increased systemic and local circulation across four cancer types. We will also test whether atorvastatin, a cholesterol-lowering drug, would further enhance the effects of exercise. We hypothesize that a combined intervention of increased physical activity and atorvastatin may reduce tumour hypoxia. We will also explore associations between changes in tumour hypoxia and clinical outcomes during oncological treatment. Methods The MOVES study is an open-label, randomized, controlled trial. It enrolls 400 adult patients with advanced cancer (prostate, breast, renal, or ovarian) who initiate first-line standard-of-care oncological treatment. Statin-naïve participants are randomized between three arms: (1) supervised exercise with atorvastatin (40 mg once daily) for three months, (2) supervised exercise without atorvastatin, or (3) unsupervised voluntary exercise. Participants who already use statins at the time of recruitment are randomized into two arms: supervised exercise or unsupervised voluntary exercise. The follow-up period extends for 24 months. Outcomes The study will assess tumour hypoxia in primary tumours and metastases using EF5-PET imaging, as well as tumour metabolic activity measured by FDG-PET. Additional assessments include circulating biomarkers of hypoxia and metabolism, tolerability of oncological treatments, body composition, physical performance, quality of life, depressive symptoms, nutritional status, cancer-related pain, personal relationships, progression-free survival, and overall survival. This randomized exploratory study will characterize the tumour-agnostic effects of exercise and metabolic modulation with atorvastatin on tumour hypoxia. Results from the trial will be published in international peer-reviewed journals following study completion, contributing valuable insights into the potential integration of exercise and statin therapy in cancer care.