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The pathobiology of mucositis

Key Points

  • Mucositis is a common toxicity of antineoplastic radiation and drug therapies, and is associated with several adverse symptomatic, health and economic outcomes.

  • There is no effective way to prevent or treat mucositis at present.

  • Understanding of the pathobiology of mucositis has increased rapidly during the past decade.

  • Mucositis is a biologically complex process that involves a dynamic, interactive sequence of panmucosal events that ultimately targets epithelial stem cells.

  • Several mechanistically based anti-mucositis agents are in development.

  • It is unlikely that a single drug or biological agent will meet the needs of all patients. Rather, the choice of the interventional agent that is used will depend on a range of factors that are related to the patient and to the particular cancer therapy they are receiving.


Oral and gastrointestinal mucositis is a toxicity of many forms of radiotherapy and chemotherapy. It has a significant impact on health, quality of life and economic outcomes that are associated with treatment. It also indirectly affects the success of antineoplastic therapy by limiting the ability of patients to tolerate optimal tumoricidal treatment. The complex pathogenesis of mucositis has only recently been appreciated and reflects the dynamic interactions of all of the cell and tissue types that comprise the epithelium and submucosa. The identification of the molecular events that lead to treatment-induced mucosal injury has provided targets for mechanistically based interventions to prevent and treat mucositis.

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Figure 1: The oral mucosa.
Figure 2: Primary damage response and signal amplification.
Figure 3: Ulceration and healing.
Figure 4: Signal amplification during mucositis.


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Competing interests

Stephen T. Sonis is a consultant for Biomodels LLC and its affiliates, which carry out contract research for several pharmaceutical and biotechnology companies.

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nasopharyngeal cancer

oral cavity cancer

oropharyngeal cancer

salivary gland cancer





caspase 3






















Refers to redness of the oral mucosa that characterizes the early stages of mucositis. Typically, this stage of mucositis is mildly symptomatic, with patients complaining of sensitivity similar to that of a food-induced burn.


Intravenous feeding of patients who are unable to eat, providing complete nutrition.


Radiation or chemotherapy that results in oral mucositis.


Therapeutic radiation for head and neck cancer is delivered by multiple (fractionated) small doses given over a long period of time. For example, the conventional radiation plan for tongue cancer might consist of a total dose of 70 Gy administered in 2-Gy fractions 5 days per week for 7 weeks.


Many forms of chemotherapy have the potential to non-specifically target bone-marrow stem cells. As a consequence, the normal production of neutrophils and platelets is retarded. A significant reduction in peripheral-blood neutrophils renders patients neutropenic.


A compound that show normal tissue protection from radiation by free-radical scavenging.


Bone-marrow transplants can be given following aggressive myeloablative radiation and/or chemotherapy. Autologous transplants are those in which marrow harvested from a patient is then treated and reinfused. Allotransplants are those in which marrow is harvested from another individual and than transfused into the recipient.

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Sonis, S. The pathobiology of mucositis. Nat Rev Cancer 4, 277–284 (2004).

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