Thelowergeneticlimitofcancerriskforagivenindividualissubstantiallyelevatedwithexposureto‘genotoxic’lifestylebehaviourssuchassmoking,excesscaloricintakeandlowphysicalactivityorenergyexpenditure1,2.Thisnotionisperhapsmostclearlyillustratedbytheprofounddeleteriousconsequencesofsmokingandexposuretoultravioletlightontheincidenceoflungcancerandmalignantmelanoma,respectively3–5.Ifsuchgenotoxiclifestylebehavioursacceleratethepathogenesisofcancer,thenitstandstoreasonthattheoppositemightalsobetrue—exposureto‘physiological’lifestylebehavioursmightpreventand/ordelaycarcinogenesis.Approximatelytwomillionyearsago,selectivepressuresonearlyhumanspeciesofthegenusHomoledtotheemergenceof‘stridingbipedalism’,auniqueadaptationthatbestowedhumanswiththecapacityforlong-distancewalkingandendurancerunning,anobligatoryrequirementforeffectivescavenging,avoidanceofpredationandpersistenthunting2,6,7.Overthenextone(office-basedvocations)inthetwentiethcenturyhascausedamarkeddeclineinphysicalactivity.Despitetheserecentglobalshifts,individualswhomaintainalifestylewithhighmobilityandphysicalactivityappeartohavearemarkablylowerriskofnon-communicablediseases,includingcancer9–11,17,18.Overthepast30years,numerousobservationalstudieshaveshownthatexposuretochronicexercisestronglyreducestheriskoftheprimarydevelopmentofmanycancers19.Inaddition,initialdatapublishedoverthepastdecadesuggestthatexposuretoexercisefollowingthediagnosisofcertainsolidtumoursmightlowertheprogressionofdiseaseandreducecancer-relatedmortality20.However,themolecularmechanismsthatunderpinthepotentialantitumoureffectsofexercisearepoorlyunderstood21,22.InthisOpinionarticle,weexploretheputativeeffectsofexerciseonreprogrammingtheinteractionbetweenthehostandthetumourmicroenvironment(TME).First,weprovideanoverviewofthephysiologicaladaptationstoexerciseintissue-relevantbiologicalprocesses(includingmetabolic,angiogenicandimmuneresponses)inskeletalmuscle.Wethendiscusshowthesechanges,alongwithchangesinothertissuesthatareprimarilyimplica...
