Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial

Strojan, Primoz; Plavc, Gaber; Kokalj, Marko; Mitrovic, Goran; Blatnik, Olga; Lezaic, Luka; Socan, Aljaz; Bavec, Aljosa; Tesic, Natasa; Hartman, Katrina; Svajger, Urban

doi:10.2478/raon-2023-0052

Cited by 3 publications

(4 citation statements)

References 45 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it should be clearly emphasized that the remainder of the works, of varying methodologies, focus on the use of MSCs of various origins for treating irradiation-induced salivary dysfunction, such as hyposalivation and xerostomia/dry mouth in patients with head and neck cancers (for instance PROSPERO CRD42021227336, NCT04489732, NCT047765392, NCT03874572, MESRIX-SAFE, MESRIX, MESRIX-II and MESRIX-III studies). The above-mentioned works will be discussed in the next section [202][203][204][205][206][207][208][209][210][211][212][213][214].…”

Section: The Pharmacological Strategies Of Msc-based Treatment For Hu...mentioning

confidence: 99%

“…These properties make the cells a very promising direction of research for use in anti-cancer therapy and as a source of cells that can promote the regeneration of the salivary gland parenchyma and restore radiation-induced damage. Unfortunately, despite progress in various preclinical in vivo models and human studies, only a few publications have examined the use of MSC transplantation as a potentially curative treatment option in HNC [202][203][204][205][206][207][208][209][210][211][212][213][214].…”

Section: The Pharmacological Strategies Of Msc-based Treatment For Hncmentioning

confidence: 99%

“…It should be noted that all existing prospective, randomized and controlled preclinical in vitro and animal models and clinical in vivo or human tissue studies, evaluate the use of MSCs derived from various origins for treating irradiation-induced salivary dysfunction (MARSH) and xerostomia (RIX) in specific head and neck cancers [202][203][204][205][206][207][208][209][210][211][212][213][214]. Many of these are reviewed in the present paper, particularly those concerning radiotherapy-induced xerostomia, e.g., the PROSPERO study (www.crd.ac.uk/prospero), registration number CRD42021227336, and I/II phase clinical studies such as NCT04489732, NCT047765392, NCT03874572 [202][203][204][205][206][207][208][209][210][211][212][213][214]. However, as an analysis of all available publications exceeds the scope of this study, only the most interesting and promising articles were included, based on data obtained from ClinicalTrials.gov., U.S. National Library of Medicine (available on April 30, 2024) and PubMed/Medline/EMBASE Library database and Cochrane Database of Systematic Reviews.…”

Section: The Pharmacological Strategies Of Msc-based Treatment For Hncmentioning

confidence: 99%

“…This open-label clinical study confirmed the safety and feasibility of local submandibular gland therapy with use of the autologous adipose-derived mesenchymal stem cells from healthy donors in previous oropharynx cancer patients. A nonrandomized, open-label, phase I exploratory study by Strojan et al also examined the positive impact of MSC-based therapy as a potential medical procedure in patients with head and neck tumours [205]. The researchers present a trial clinical protocol used to evaluate the safety and preliminary efficacy of allogeneic MSCs derived from human umbilical cord tissue (hUC-MSCs).…”

Section: The Pharmacological Strategies Of Msc-based Treatment For Hncmentioning

confidence: 99%

See 3 more Smart Citations

The Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer – Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of the Use of Stromal Cell-Based Pharmacological Strategies

Starska-Kowarska

2024

Preprint

View full text Add to dashboard Cite

The most common type of head and neck cancer (HNC) is head and neck squamous cell carcinoma (HNSCC). It describes a heterogenous neoplastic disease that arises from the mucosal epithelium of the of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being is the eighth most common cancer worldwide, with 931,931 newly diagnosed cases and 467,125 deaths according to the latest Global Cancer Statistics (GLOBOCAN) data. Despite the use of modern low-invasive surgical techniques and application of promising new chemoradiotherapies or combination treatment, the frequency of recurrences and the five-year survival of these patients remains unsatisfactory. The microenvironment of head and neck cancer comprises various cells that regulate neoplastic expansion. It is believed that the mesenchymal stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and progression, in the regulation of cancer treatment response, survival rates, patient outcomes and long-term prognosis; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNSCC. MSCs, are multipotent, heterogeneous, mobile cells, which meet specific stemness criteria defined by the International Society for Cellular Therapy (ISCT). Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties, they may play a key role in the process of acquiring drug resistance, and thus treatment failure. MSCs must also demonstrate plastic adherence in vitro and be able to differentiate into specific mesodermal cell types after stimulation i.e., adipocytes, chondrocytes, and osteoblasts when cultured under well-defined conditions. The present narrative review examines the links between mesenchymal stromal/stem cells and HNC, as well as the different mechanisms involved in the development of resistance to current chemo- and radiotherapies in HNSCC. It provides an overview of the current literature, including key opinion-forming systematic reviews, as well as cross-sectional, longitudinal, prospective and interventional studies based on cell culture models in vitro, animal or in vivo models of HNSCC; it also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. The data concerning tumour-associated MSCs is arranged according to increasing clinical credibility.

show abstract

Section: The Pharmacological Strategies Of Msc-based Treatment For Hu...mentioning

confidence: 99%

Section: The Pharmacological Strategies Of Msc-based Treatment For Hncmentioning

confidence: 99%

Section: The Pharmacological Strategies Of Msc-based Treatment For Hncmentioning

confidence: 99%

Section: The Pharmacological Strategies Of Msc-based Treatment For Hncmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer – Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of the Use of Stromal Cell-Based Pharmacological Strategies

Starska-Kowarska

2024

Preprint

View full text Add to dashboard Cite

show abstract

Chronic Phenotypes Underlying Radiation-Induced Salivary Gland Dysfunction

Gunning,

Limesand

2024

J Dent Res

View full text Add to dashboard Cite

Head and neck cancer (HNC) is the sixth most diagnosed cancer, and treatment typically consists of surgical removal of the tumor followed by ionizing radiation (IR). While excellent at controlling tumor growth, IR often damages salivary glands due to their proximity to common tumor sites. Radiation damage to salivary glands results in loss of secretory function, causing severe and chronic reductions in salivary flow. This leads to the patient-reported sensation of dry mouth, termed xerostomia, which significantly reduces quality of life for HNC patients and survivors. The mechanisms underlying salivary gland damage remain elusive, and therefore, treatment options are scarce. Available therapies provide temporary symptom relief, but there is no standard of care for permanent restoration of function. There is a significant gap in understanding the chronic mechanistic responses to radiation as well as treatments that can be given in the months to years following cessation of treatment. HNC cases are steadily rising; particularly, the number of young patients diagnosed with nonfatal human papillomavirus + HNC continues to increase. The growing number of HNC diagnoses and improved prognoses results in more people living with xerostomia, which highlights the mounting need for restorative treatments. Mechanisms underlying chronic damage include decreases in acinar differentiation markers, increases in acinar cell proliferation, immune and inflammatory dysregulation, and metabolic changes including increases in amino acids and reductions in glycolysis and oxidative phosphorylation, fibrosis, and dysregulated neuronal responses. Currently, promising treatment options include adenoviral gene transfers and stem cell therapy. Thus, this review describes in depth known mechanisms contributing to chronic damage and discusses therapeutic advances in treating chronically damaged glands. Understanding the chronic response to radiation offers potential in development of new therapeutics to reverse salivary gland damage and improve the quality of life of HNC survivors.

show abstract

Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer—Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of Stromal Cell-Based Pharmacological Strategies

Starska-Kowarska

2024

Cells

View full text Add to dashboard Cite

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC.

show abstract

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial

Cited by 3 publications

References 45 publications

The Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer – Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of the Use of Stromal Cell-Based Pharmacological Strategies

The Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer – Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of the Use of Stromal Cell-Based Pharmacological Strategies

Chronic Phenotypes Underlying Radiation-Induced Salivary Gland Dysfunction

Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer—Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of Stromal Cell-Based Pharmacological Strategies

Contact Info

Product

Resources

About