An update on pharmacotherapies in active development for the management of cancer regimen-associated oral mucositis

Abstract 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…

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Could the biological robustness of low-level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients

Abstract Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our investigation identified a substantial number of LLLT-activated pathways…

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Exploring Genetic Attributions Underlying Radiotherapy-Induced Fatigue in Prostate Cancer Patients

Abstract Context: Despite numerous proposed mechanisms, no definitive pathophysiology underlying radiotherapy-induced fatigue (RIF) has been established. However, the dysregulation of a set of 35 genes was recently validated to predict development of fatigue in prostate cancer patients receiving radiotherapy. Objectives: To hypothesize novel pathways, and provide genetic targets for currently proposed pathways implicated in RIF development through…

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Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Abstract The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft-versus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign…

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Pharmacotherapy for the management of cancer regimen-related oral mucositis

ABSTRACT Introduction: Oral mucositis is a frequent and devastating toxicity secondary to cancer treatment, which may affect 20–40% of patients receiving conventional chemotherapy and 60–85% of patients undergoing hematopoietic stem cell transplantation. The pathobiology of mucositis includes a complex cascade of biologic events in which pro-inflammatory cytokines, ROS, second messengers, and the oral microbiome contribute…

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New Frontiers in the Pathobiology and Treatment of Cancer Regimen-Related Mucosal Injury

Mucositis is a common complication of chemotherapy, radiotherapy and targeted agents. It often affects compliance to anticancer therapies as it frequently causes schedule delays, interruptions or discontinuations of treatment. Moreover, the economic impact related to the management of mucositis is topical and several estimations of additional hospital costs due to this clinical condition have been…

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Predicting mucositis risk associated with cytotoxic cancer treatment regimens: rationale, complexity, and challenges

Abstract Purpose of review: The goals of this review are to describe the complexity of factors influencing the risk of cancer regimen-related mucosal injury (CRRMI), to evaluate the contribution of the innate immune response to CRRMI risk, to compare the concordance of genome analytics in describing mechanism and risk, and to determine if common biological pathways…

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Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or Oropharyngeal Carcinoma

Abstract Purpose: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM). Patients and methods: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation…

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Host-Microbiome Cross-talk in Oral Mucositis

Abstract 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…

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Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer

Abstract Purpose: Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC.…

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Phase II investigational oral drugs for the treatment of radio/chemotherapy induced oral mucositis

Abstract Introduction: Oral mucositis is a significant unmet clinical need for many cancer patients. The biological complexity of mucositis’ pathogenesis provides a number of mechanistic targets suitable as pharmacologic targets. The diversity of targets has stimulated drug development in search of an effective intervention. In this paper, we review a range of agents that are currently…

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