title: The potential role of aerobic exercise to modulate cardiotoxicity of molecularly targeted cancer therapeutics.
abstract: Molecularly targeted therapeutics (MTT) are the future of cancer systemic therapy. They have already moved from palliative therapy for advanced solid malignancies into the setting of curative-intent treatment for early-stage disease. Cardiotoxicity is a frequent and potentially serious adverse complication of some targeted therapies, leading to a broad range of potentially life-threatening complications, therapy discontinuation, and poor quality of life. Low-cost pleiotropic interventions are therefore urgently required to effectively prevent and/or treat MTT-induced cardiotoxicity. Aerobic exercise therapy has the unique capacity to modulate, without toxicity, multiple gene expression pathways in several organ systems, including a plethora of cardiac-specific molecular and cell-signaling pathways implicated in MTT-induced cardiac toxicity. In this review, we examine the molecular signaling of antiangiogenic and HER2-directed therapies that may underpin cardiac toxicity and the hypothesized molecular mechanisms underlying the cardioprotective properties of aerobic exercise. It is hoped that this knowledge can be used to maximize the benefits of small molecule inhibitors, while minimizing cardiac damage in patients with solid malignancies.
authors: Exercise Physiology and Countermeasures, NASA Johnson Space Center, Universities Space Research Association, 2101 NASA Parkway, Houston, TX 77058, USA. jessica.m.scott@nasa.gov
authors: Jessica M
authors: JM
authors: Scott
authors: Susan
authors: S
authors: Lakoski
authors: John R
authors: JR
authors: Mackey
authors: Pamela S
authors: PS
authors: Douglas
authors: Mark J
authors: MJ
authors: Haykowsky
authors: Lee W
authors: LW
authors: Jones
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015444:Exercise / Q000502:physiology*; D006331:Heart Diseases / Q000139:chemically induced* / Q000628:therapy*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human