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Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities
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Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (25 August 2023) | Viewed by 9949

Special Issue Editor

Dr. Stephen T. Sonis

E-Mail Website
Guest Editor
1. Divisions of Oral Medicine, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston, MA 02114, USA
2. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02114, USA
Interests: stomatitis; mucositis; cancer, radiation; chemotherapy; targeted therapy; immunotherapy; pathogenesis; treatment

Special Issue Information

Dear Colleagues,

Thank you for agreeing to contribute to this Special Issue of IJMS. We hope that our papers will be informative and provocative, and will cumulatively catalyze interest and investigation.  As we all know, the oral mucosa has been a consistent target for collateral damage associated with almost all forms of cancer therapy. The negative outcomes associated with regimen-related mucositis and stomatitis are associated with a significant symptom burden, the inability of patients to tolerate optimum anti-cancer therapy, and higher healthcare resource use and costs. Improved understanding of the pathobiology leading to oral mucosal injury continues to evolve, although there is still much to be learned. This is true, not only of mucositis associated with conventional cytotoxic therapies, but is also increasingly important for targeted and immunotherapies. The anatomic and environmental diversity of the mouth—including multiple epithelia, hard tissue, microbiome, and fluidics—provides a platform for this. This Special Issue aims to highlight current knowledge of mucositis/stomatitis pathogenesis and pathobiology, discuss critical gaps in knowledge and how they may be most effectively studied, and provide conceptual application of the underlying science to the development of potential interventional strategies.

I look forward to your contributions. 

Thank you.

Dr. Stephen T. Sonis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stomatitis
  • mucositis
  • cancer
  • radiation
  • chemotherapy
  • targeted therapy
  • immunotherapy
  • pathogenesis
  • treatment

Published Papers (5 papers)

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Review

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16 pages, 900 KiB  
Review
Attempts to Understand Oral Mucositis in Head and Neck Cancer Patients through Omics Studies: A Narrative Review
by Erin Marie D. San Valentin, Kim-Anh Do, Sai-Ching J. Yeung and Cielito C. Reyes-Gibby
Int. J. Mol. Sci. 2023, 24(23), 16995; https://doi.org/10.3390/ijms242316995 - 30 Nov 2023
Viewed by 1041
Abstract
Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, [...] Read more.
Oral mucositis (OM) is a common and clinically impactful side effect of cytotoxic cancer treatment, particularly in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy with or without concomitant chemotherapy. The etiology and pathogenic mechanisms of OM are complex, multifaceted and elicit both direct and indirect damage to the mucosa. In this narrative review, we describe studies that use various omics methodologies (genomics, transcriptomics, microbiomics and metabolomics) in attempts to elucidate the biological pathways associated with the development or severity of OM. Integrating different omics into multi-omics approaches carries the potential to discover links among host factors (genomics), host responses (transcriptomics, metabolomics), and the local environment (microbiomics). Full article
(This article belongs to the Special Issue Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities)
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14 pages, 844 KiB  
Review
The Role of the Innate Immune Response in Oral Mucositis Pathogenesis
by Joanne Bowen and Courtney Cross
Int. J. Mol. Sci. 2023, 24(22), 16314; https://doi.org/10.3390/ijms242216314 - 14 Nov 2023
Cited by 1 | Viewed by 1172
Abstract
Oral mucositis (OM) is a significant complication of cancer therapy with limited management strategies. Whilst inflammation is a central feature of destructive and ultimately ulcerative pathology, to date, attempts to mitigate damage via this mechanism have proven limited. A relatively underexamined aspect of [...] Read more.
Oral mucositis (OM) is a significant complication of cancer therapy with limited management strategies. Whilst inflammation is a central feature of destructive and ultimately ulcerative pathology, to date, attempts to mitigate damage via this mechanism have proven limited. A relatively underexamined aspect of OM development is the contribution of elements of the innate immune system. In particular, the role played by barriers, pattern recognition systems, and microbial composition in early damage signaling requires further investigation. As such, this review highlights the innate immune response as a potential focus for research to better understand OM pathogenesis and development of interventions for patients treated with radiotherapy and chemotherapy. Future areas of evaluation include manipulation of microbial–mucosal interactions to alter cytotoxic sensitivity, use of germ-free models, and translation of innate immune-targeted agents interrogated for mucosal injury in other regions of the alimentary canal into OM-based clinical trials. Full article
(This article belongs to the Special Issue Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities)
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17 pages, 1157 KiB  
Review
From Pathogenesis to Intervention: The Importance of the Microbiome in Oral Mucositis
by Julia S. Bruno, Ghanyah H. Al-Qadami, Alexa M. G. A. Laheij, Paolo Bossi, Eduardo R. Fregnani and Hannah R. Wardill
Int. J. Mol. Sci. 2023, 24(9), 8274; https://doi.org/10.3390/ijms24098274 - 5 May 2023
Cited by 7 | Viewed by 2915
Abstract
Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a [...] Read more.
Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a hostile environment for resident microbes, with oral infections co-occurring with OM, especially at sites of ulceration. Increasing evidence suggests that oral microbiome changes occur beyond opportunistic infection, with a growing appreciation for the potential role of the microbiome in OM development and severity. This review collects the latest articles indexed in the PubMed electronic database which analyse the bacterial shift through 16S rRNA gene sequencing methodology in cancer patients under treatment with oral mucositis. The aims are to assess whether changes in the oral and gut microbiome causally contribute to oral mucositis or if they are simply a consequence of the mucosal injury. Further, we explore the emerging role of a patient’s microbial fingerprint in OM development and prediction. The maintenance of resident bacteria via microbial target therapy is under constant improvement and should be considered in the OM treatment. Full article
(This article belongs to the Special Issue Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities)
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13 pages, 295 KiB  
Review
Pathogenesis of Oral Toxicities Associated with Targeted Therapy and Immunotherapy
by Alessandro Villa and Michal Kuten-Shorrer
Int. J. Mol. Sci. 2023, 24(9), 8188; https://doi.org/10.3390/ijms24098188 - 3 May 2023
Cited by 4 | Viewed by 2391
Abstract
Targeted therapy and immunotherapy have redefined cancer treatment. While they have enhanced tumor response and improved survival rates in many cancer types, toxicities continue to occur, and these often involve the oral cavity. Broadly reported as “mucositis” or “stomatitis,” oral toxicities induced by [...] Read more.
Targeted therapy and immunotherapy have redefined cancer treatment. While they have enhanced tumor response and improved survival rates in many cancer types, toxicities continue to occur, and these often involve the oral cavity. Broadly reported as “mucositis” or “stomatitis,” oral toxicities induced by targeted therapies differ clinically and mechanistically from those associated with conventional chemotherapy. Manifesting primarily as mucosal lesions, salivary gland hypofunction, or orofacial neuropathies, these oral toxicities may nonetheless lead to significant morbidity and impact patients’ quality of life, thereby compromising clinical outcomes. We conclude that familiarity with the spectrum of associated toxicities and understanding of their pathogenesis represent important areas of clinical research and may lead to better characterization, prevention, and management of these adverse events. Full article
(This article belongs to the Special Issue Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities)

Other

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18 pages, 973 KiB  
Perspective
Mucositis and Infection in Hematology Patients
by Nicole M. A. Blijlevens and Charlotte E. M. de Mooij
Int. J. Mol. Sci. 2023, 24(11), 9592; https://doi.org/10.3390/ijms24119592 - 31 May 2023
Cited by 2 | Viewed by 1809
Abstract
Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. [...] Read more.
Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advances in our understanding of the relation of mucositis and infection. Full article
(This article belongs to the Special Issue Cancer Treatment Regimen-Related Oral Mucosal Injury: Pathogenesis and Therapeutic Opportunities)
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