GI Toxicity and Mucositis
Epistem offers gold standard in vivo mucositis models to test the efficacy of anti-mucositis therapeutic agents. These models can also be used to assess the likelihood of a novel therapeutic agent causing mucositis and can help devise dosing strategies to minimise toxicity. Epistem's mucositis team have been working in this area for over 20 years. During this time, Epistem has been involved with the pre-clinical development of many candidate therapies.
Chemotherapy and radiotherapy are the most common and effective oncology therapies but adversely affect healthy tissue. Systemic chemotherapy can cause painful and dose limiting ulceration of both the intestine and oral mucosa. Treatment with focal radiotherapy, commonly used for head and neck, large bowel and prostate cancer, can cause similar oral or colonic lesions.
The cells lining the crypts of the small intestine are the most rapidly proliferating in the body and therefore particularly sensitive to interruption in cell proliferation caused by oncology therapy. If the stem cells within the intestinal crypts are killed, ulceration can occur resulting in diarrhoea, dehydration and infection. Cell turnover in the oral cavity is slower than in the small intestine, oral ulcers are therefore slower to manifest. Oral ulcers are very painful and of great clinical concern; due to lack of patient compliance oncology therapy can be withdrawn, or treatment intensity reduced to prevent further damage.
An important consideration in the development of anti-mucositis therapeutics is that the novel therapeutic agent must not protect tumours or promote tumour growth. Epistem have the capabilities to evaluate the effect of a therapeutic agent on tumour growth using xenograft models.
Epistem can perform GLP compliant studies where required using a 320kV X ray which enables total or partial body irradiation, mimicking a clinically relevant insult.