The pathophysiology of<unk>  is complex and multifactorial. Currently, Sonis' five phase model is the accepted explanation for the process. The 5 stages are: # Initiation phase. Free radicals are produced due to DNA damage caused by chemo- or radiotherapy. # Primary damage response. Chemotherapy, radiotherapy and free radicals all contribute to the activation of transcription factors, such as NF-κB. This results in the upregulation of pro-inflammatory cytokines, ceramide, nitric oxide and matrix metalloproteinases. The consequence of this is mucosal destruction, caused by thinning of the epithelium due to tissue injury and cell death. # Signal amplification. Positive or negative feedback loops involving some of the molecules in the previous phase can exacerbate or prolong tissue injury. For example, the pro-inflammatory cytokine TNF-α can positively feedback on NF-κB thus inducing more pro-inflammatory cytokine production. # Ulceration. Bacteria colonise ulcers and their cell wall products infiltrate the submucosa. This leads to activation of tissue macrophages, which causes further production of pro-inflammatory cytokines. In addition, bacteria-mediated immune signalling via Toll-like receptors (TLRs) ambiguously shapes chemotherapy-induced genotoxic damage in the gastrointestinal tract. # Healing. Signalling from the extracellular matrix of the submucosa results in epithelial proliferation and differentiation, and thus a thickening of the epithelium. The local oral flora are reinstated.
Mucositis
Serositis
Myositis
Photosensitivity
Dermatitis
Arthropathy
Leukoedema
Enteropathy