Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen–related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention.

Fibrosis is a common, persistent and potentially debilitating complication of chemotherapy and radiation regimens used for the treatment of cancer. The molecular mechanisms underlying fibrosis have been well studied and reveal overall processes that are largely ubiquitous. However it is important to note that although the processes are similar, they result in cellular phenotypes that are highly tissue specific. These tissue specific differences may present opportunities for therapeutic interventions to prevent or treat this often irreversible condition. Data generated from animal models of cancer therapy-related tissue toxicities have revealed that the signaling pathways involved in fibrosis are the same as those involved in the normal injury response and include the TGFb superfamily and a range of pro-inflammatory cytokines. The critical difference between normal wound healing and fibrosis development appears to be, that in fibrosis, these signaling pathways escape normal cellular regulation. As a result, an injury state is maintained and processes involved in normal healing are usurped. There are a few, if any, therapeutics that effectively prevent or treat fibrosis in patients. Consequently, cancer survivors may be chronically plagued with a variety of life-altering fibrosis-related symptoms. Uncovering the signaling pathways that drive cellular fibrosis is paramount to the development of specific therapeutics that will mitigate this potentially devastating condition.

Background: Fatigue is a common side effect of cancer (CA) treatment. We used a novel analytical method to identify and validate a specific gene cluster that is predictive of fatigue risk in prostate cancer patients (PCP) treated with radiotherapy (RT). Methods: A total of 44 PCP were categorized into high-fatigue (HF) and low-fatigue (LF) cohorts based on fatigue score change from baseline to RT completion. Fold-change differential and Fisher's linear discriminant analyses (LDA) from 27 subjects with gene expression data at baseline and RT completion generated a reduced base of most discriminatory genes (learning phase). A nearest-neighbor risk (k-NN) prediction model was developed based on small-scale prognostic signatures. The predictive model validity was tested in another 17 subjects using baseline gene expression data (validation phase). Result: The model generated in the learning phase predicted HF classification at RT completion in the validation phase with 76.5% accuracy. Conclusion: The results suggest that a novel analytical algorithm that incorporates fold-change differential analysis, LDA, and a k-NN may have applicability in predicting regimen-related toxicity in cancer patients with high reliability, if we take into account these results and the limited amount of data that we had at disposal. It is expected that the accuracy will be improved by increasing data sampling in the learning phase.

Oral mucositis (OM) remains a significant unmet need for patients being treated with standard concomitant chemoradiation (CRT) regimens for head and neck cancers (HNC). OM’s pathogenesis is complex and includes both direct and indirect damage pathways. In this paper, the field is reviewed with emphasis on the initiating and sustaining role of oxidative stress on OM’s pathobiology. A hypothesis is presented which suggests that based on OM’s clinical and biological trajectory, mucosal damage is largely the consequence of cumulative CRT-induced biological changes overwhelming physiologic self-protective mechanisms. Furthermore, an individual’s ability to mount and maintain a protective response is dependent on interacting pathways which are primarily determined by a multiplex consisting of genomics, epigenomics, and microbiomics. Effective biologic or pharmacologic OM interventions are likely to supplement or stimulate existing physiologic damage-control mechanisms.

Introduction: Oral mucositis (OM) is a common toxicity of cytotoxic cancer regimens and remains one of the most painful, injurious, and treatment-disrupting side effects of radiation and ablative therapy. Despite its frequency and impact, approved definitive preventive or therapeutic options remain limited. Areas covered: This review focuses on mechanistically active small molecules and biologicals that are under clinical development for the prevention of oral mucositis. The authors have excluded those compounds and devices for which their indication is limited to symptoms management. Expert opinion: OM remains a significant unmet clinical need. The commercial opportunities for an effective treatment have been characterized as a global market of $1 billion (US). The formulations of drugs under development vary considerably but share some several commonalities in their development scheme. All new agents are given prophylactically and are being evaluated in patients treated with concomitant chemoradiation therapy for head and neck cancer. The primary efficacy outcome for most trials is dependent on the assessment of mucositis using the scoring scale established years ago by the World Health Organization. The development activity for OM is robust with a diverse range of agents. New drug applications for effective therapeutic options for OM should be ready for review within the next few years.