TY - JOUR

T1 - Animal models of chemotherapy-induced mucositis

T2 - Translational relevance and challenges

AU - Sangild, Per T.

AU - Shen, René Liang

AU - Pontoppidan, Peter

AU - Rathe, Mathias

PY - 2018

Y1 - 2018

N2 - Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs, and several animal models of CIM have been developed, mainly in rodents and piglets, to help understand the progression of CIM and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g., GIT) insights, standardized, clinically relevant treatment regimens, and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM management and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients, which vary according to the antineoplastic drugs, dose, underlying (cancer) disease, and patient characteristics (e.g., age, genetics, and body constitution). Another factor that hinders the direct use of results from animals is inadequate collaboration between basic science and clinical science in relation to CIM. Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g., milk fractions, colostrum, and plant extracts), nutrients (e.g., polyunsaturated fatty acids, short-chain fatty acids, and glutamine), and growth factor peptides (e.g., transforming growth factor and glucagon-like peptide-2), as well as manipulations of the gut microbiota (e.g., prebiotics, probiotics, and antibiotics). Rodent CIM models allow well-controlled, in-depth studies of animals with or without tumors while pig models more easily make clinically relevant treatment regimens possible. In synergy, animal models of CIM provide the basic physiological understanding and the new ideas for treatment that are required to make competent decisions in clinical practice.

AB - Chemotherapy for cancer patients induces damaging tissue reactions along the epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced mucositis (CIM) is a serious side effect of cytotoxic drugs, and several animal models of CIM have been developed, mainly in rodents and piglets, to help understand the progression of CIM and how to prevent it. Animal models allow highly controlled experimental conditions, detailed organ (e.g., GIT) insights, standardized, clinically relevant treatment regimens, and discovery of new biomarkers. Still, surprisingly few results from animal models have been translated into clinical CIM management and treatments. The results obtained from specific animal models can be difficult to translate to the diverse range of CIM manifestations in patients, which vary according to the antineoplastic drugs, dose, underlying (cancer) disease, and patient characteristics (e.g., age, genetics, and body constitution). Another factor that hinders the direct use of results from animals is inadequate collaboration between basic science and clinical science in relation to CIM. Here, we briefly describe CIM pathophysiology, particularly the basic knowledge that has been obtained from CIM animal models. These model studies have indicated potential new preventive and ameliorating interventions, including supplementation with natural bioactive diets (e.g., milk fractions, colostrum, and plant extracts), nutrients (e.g., polyunsaturated fatty acids, short-chain fatty acids, and glutamine), and growth factor peptides (e.g., transforming growth factor and glucagon-like peptide-2), as well as manipulations of the gut microbiota (e.g., prebiotics, probiotics, and antibiotics). Rodent CIM models allow well-controlled, in-depth studies of animals with or without tumors while pig models more easily make clinically relevant treatment regimens possible. In synergy, animal models of CIM provide the basic physiological understanding and the new ideas for treatment that are required to make competent decisions in clinical practice.

KW - Chemotherapy

KW - Inflammation

KW - Intestine

KW - Mice

KW - Mucositis

KW - Pig

KW - Rat

KW - Toxicity

U2 - 10.1152/ajpgi.00204.2017

DO - 10.1152/ajpgi.00204.2017

M3 - Journal article

C2 - 29074485

AN - SCOPUS:85043577564

VL - 314

SP - G231-G246

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 2

ER -