Exercise, cancer, and the cardiovascular system: clinical effects and mechanistic insights

Figures

• 

  Fig. 1. Limitations of oxygen transfer from the upper airways to the mitochondrion in cancer patients and associated clinical symptoms. Created with BioRender.com

• 

  Fig. 2. Differential molecular regulation of cancer cells. Cancer stem cells and bulk cancer cells display differential properties of intracellular communication. PGC-1α: Peroxisome proliferator-activated receptor gamma co-activator-1alpha. ROS: Reactive oxygen species

• 

  Fig. 3. Selected exercise-induced molecular mechanisms in skeletal muscle cells. Exercise activates the central player (in bold) peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1α), which in turn facilitates the upregulation of calcium–calmodulin-dependent kinase (caMK) and 5`-adenomonophosphate-activated protein kinase (AMPK). Furthermore, p38 mitogen-activated protein kinase (p38 MAPK) is activated leading to an increase of mitochondrial synthesis. To stimulate autophagy of mitochondria and lysosomes, AMPK triggers activation of Unc-51 like autophagy activating kinase 1 (ULK 1). In addition, PGC-1α stimulates nuclear respiratory factor (NRF 1/2), which activates mitochondrial transcription factor A (tfam) and also results in enhanced mitochondrial synthesis. Furthermore, exercise facilitates modulation of reactive oxygen species (ROS), heat shock protein 60 (HSP 60), and upregulation of enzymes of the tricarboxylic acid cycle (TCA) and the respiratory chain (RCE)

• 

  Fig. 4. Components of physical fitness. Physical fitness is a state of multiple components, only one of which is cardiac function

• 

  Fig. 5. Exercise limitations of cancer patients. Cancer patients display reduced cardiorespiratory fitness (CRF) expressed through reduced peak oxygen consumption (VO2peak), which is often facilitated by cachexia and/or cancer-induced immobility. VO2peak reduction in cancer patients is a composite of lower cardiac output, stroke volume, heart rate increase, and peripheral oxygen extraction during exercise. Reduced left ventricular (LV) compliance and increased systemic vascular resistance also contribute to VO2peak reduction. Created with BioRender.com

• 

  Fig. 6. An example for a tailored exercise prescription in a breast cancer patient undergoing 12 weeks of chemotherapy and a 12-month- follow-up is provided. Exercise is performed 3x/week (30 min each) including aerobic exercise training (AET) consisting of both moderate continuous (MCT) and high-intensity exercise training (HIIT) and additional resistance training (RT). A year of training is separated into four cycles of 12 weeks each, with the first cycle integrating chemotherapy. Before each cycle cardiopulmonary exercise testing (CPET) is performed to adapt training corridors of AET. MCT is performed at 5–10 beats/min (HR, heart rate) above the first ventilatory threshold (VT1), while HIIT consists of five intense cycles with 2 min each using short bouts just below (5–10 beats/minute) the second ventilatory threshold (VT2). RT is increased in intensity over the year starting with more repetitions (rep) and lower intensities (derived from the one repetition maximum, 1 RPM). Frequency of MCT and HIIT is varied across the cycles, RT is performed 3x/week. Created with BioRender.com