Development of a rat model of oral small molecule receptor tyrosine kinase inhibitor-induced diarrhea

Bowen, Joanne M.; Mayo, Bronwen J.; Plews, Erin; Bateman, Emma; Stringer, Andrea M.; Boyle, Frances M.; Finnie, John; Keefe, Dorothy

doi:10.4161/cbt.21783

Cited by 35 publications

(42 citation statements)

References 32 publications

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“…a detailed description of the experimental protocol has been previously published [22]. Briefly, male albino Wistar rats were treated with lapatinib daily for 4 weeks via oral gavage.…”

Section: Methodsmentioning

confidence: 99%

“…Whilst the effect of egFr tKI's on neurons has yet to be studied, clinically they are not associated with neuropathy. recently, we developed a rat model of lapatinib-induced diarrhoea with the purpose of increasing understanding of tKI-induced diarrhoea mechanisms and to provide a platform to test novel diarrhoea interventions [22]. this model uses a four-week schedule of daily oral lapatinib treatment to induce mild to moderate diarrhoea in rats, whilst achieving a lapatinib C min similar to clinical studies.…”

Section: Introductionmentioning

confidence: 97%

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Determining the mechanisms of lapatinib-induced diarrhoea using a rat model

Bowen

Mayo

Plews

et al. 2014

Cancer Chemother Pharmacol

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“…a detailed description of the experimental protocol has been previously published [22]. Briefly, male albino Wistar rats were treated with lapatinib daily for 4 weeks via oral gavage.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Determining the mechanisms of lapatinib-induced diarrhoea using a rat model

Bowen

Mayo

Plews

et al. 2014

Cancer Chemother Pharmacol

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“…Animal models are currently being utilized and developed. A recently developed, clinically relevant rat model of receptor tyrosine kinase inhibitorinduced diarrhoea has already identified differences in the mechanisms of damage following targeted drugs and conventional chemotherapy agents [90]. This model is currently being utilised to determine the exact pathogenesis of lapatinib-induced diarrhoea and to evaluate potential protective strategies.…”

Section: Targeted Anti-cancer Agents and Mucosal Injurymentioning

confidence: 99%

Emerging evidence on the pathobiology of mucositis

Al‐Dasooqi

Sonis

Bowen

et al. 2013

Support Care Cancer

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169

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Background Considerable progress has been made in our understanding of the biological basis for cancer therapyinduced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. Methods Panel members reviewed the biomedical literature on mucositis pathobiology published between January 2005 and December 2011.Results Recent research has provided data on the contribution of tissue structure changes, inflammation and microbiome changes to the development of mucositis. Additional research has focused on targeted therapyinduced toxicity, toxicity clustering and the investigation of genetic polymorphisms in toxicity prediction. This review paper summarizes the recent evidence on these aspects of mucositis pathobiology. Conclusion The ultimate goal of mucositis researchers is to identify the most appropriate targets for therapeutic interventions and to be able to predict toxicity risk and personalize interventions to genetically suitable patients. Continuing research efforts are needed to further our understanding of mucositis pathobiology and the pharmacogenomics of toxicity.

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“…Recent research done in a clinically relevant rat model of tyrosine kinase inhibitor-induced diarrhea has identified that unlike with conventional chemotherapy agents, tyrosine kinase inhibitors do not cause direct damage to mucosal cells [49]. However, apart from that, the targeted agent-induced mechanism is not wellunderstood.…”

Section: Oral Toxicity Caused By Targeted Anticancer Therapymentioning

confidence: 99%

Oral Mucositis and Stomatitis Associated with Conventional and Targeted Anticancer Therapy

Parkhill¹

2013

J Pharmacovigilance

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Oral mucositis and stomatitis are characterized by pain, inflammation, and redness in the oral cavity. In the case of mucositis, ulceration also occurs. Despite being understudied, these symptoms are some of the most troubling, and yet common, adverse effects associated with cancer treatment. The incidence of these toxicities is highly variable depending on treatment-related and patient-related risk factors. However, most cancer treatment regimens carry some risk of this toxicity. The presence of mucositis or stomatitis can result in a significant decrease in the patient's quality of life due to severe pain and the inability to eat or drink. These toxicities can also negatively affect the overall outcome of cancer treatment, leading to dose reductions and delays in treatment. Although the mechanism is not yet understood, the rapid increase in the number of targeted anticancer therapies available on the market has increased the number of patients who experience oral toxicities. The toxicities caused by targeted agents are less severe than those caused by conventional anticancer agents, but due to prolonged dosing schedules, they can still lead to significant declines in quality of life. The pathobiology of oral mucositis is a complex five phase process. It involves injury, activation of enzymes and transcription factors, upregulation of cytokine genes, inflammation/damage to tissue, and healing. These processes not only involve cells in the oral mucosa, but also the surrounding fibroblasts and connective tissue cells. A better understanding of the mechanisms behind oral mucositis and stomatitis will facilitate the development of effective prediction, prevention, and treatment strategies.

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Development of a rat model of oral small molecule receptor tyrosine kinase inhibitor-induced diarrhea

Cited by 35 publications

References 32 publications

Determining the mechanisms of lapatinib-induced diarrhoea using a rat model

Determining the mechanisms of lapatinib-induced diarrhoea using a rat model

Emerging evidence on the pathobiology of mucositis

Oral Mucositis and Stomatitis Associated with Conventional and Targeted Anticancer Therapy

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