title: Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments.
abstract: Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers.
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne VIC, Australia.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McQuade
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne VIC, Australia.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Stojanovska
authors.affiliation: Área de Farmacología y Nutrición, Universidad Rey Juan CarlosMadrid, Spain; Grupo de Excelencia Investigadora URJC, Banco de Santander Grupo Multidisciplinar de Investigación y Tratamiento del Dolor, Universidad Rey Juan CarlosMadrid, Spain; Unidad Asociada al Instituto de Química Médica del Consejo Superior de Investigaciones CientíficasMadrid, Spain; Unidad Asociada al Instituto de Investigación en Ciencias de la Alimentación del Consejo Superior de Investigaciones CientíficasMadrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Abalo
authors.affiliation: Department of Physiology, University of Melbourne, Melbourne VIC, Australia.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Bornstein
authors.affiliation: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne VIC, Australia.
authors.forename: Kulmira
authors.initials: K
authors.lastname: Nurgali
keywords: chemotherapy; chemotherapy-induced constipation; chemotherapy-induced diarrhea; pathophy-siology; treatments