Thyroid disorders induced by immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs that powerfully contribute to cancer therapy by harnessing the immune system to fight malignancies. However, their successful use as anti-cancer drugs is accompanied by a wide spectrum of immune-related adverse effects (irAEs), including endocrinopathies. Among them, thyroid dysfunction stands out as one of the most common endocrinopathies induced by ICI therapy and surfaces as a prominent concern. Destructive thyroiditis is the pathophysiological basis shared by the most common patterns of thyrotoxicosis followed by hypothyroidism and isolated hypothyroidism. Diagnostic approach is guided by clinical manifestation, laboratory evaluation and imaging modalities. Treatment approaches range from the substitution of levothyroxine to the utilization of beta blockers, depending on the extent of thyroid dysfunction's severity. While the medical community is dealing with the evolution and complexities of immunotherapy, recognizing and effectively managing ICI-induced thyroid dysfunction emerged as crucial for enhancing patient safety and achieving improved outcomes. The aim of this review is to navigate the significance of ICI-induced thyroid dysfunction unraveling the various patterns, underlying mechanisms, diagnostic approaches, and treatment strategies. It, also, highlights the impact of various factors such as cancer subtype, ICI dosage, age, and genetic susceptibility on the risk of experiencing dysfunction.

An overview of the role of telomeres and telomerase in pre­neoplastic lesions (Review).

Telomeres are tandem repeats of DNA sequences protecting the end of linear chromosomes. Replicative senescence due to telomere attrition is considered a tumor-preventing mechanism in differentiated somatic cells. However, telomere shortening is associated with genome instability and several disease entities. During carcinogenesis, the development of a telomere maintenance mechanism, predominately through the activation of the telomerase enzyme, represents a hallmark of cancer, since it enables cancer cells to avert senescence and divide indefinitely. Although research of the involvement of telomeres and telomerase in various malignant neoplasms has gained a large amount of interest, the timing and relevance of their role in pre-neoplastic lesions remain to be determined. The present narrative review aims to summarize the evidence regarding the role of telomeres and telomerase in pre-neoplasia across different types of tissues.