Fotios G. Spiliopoulos

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that establishes lifelong latent infection

Lung cancer remains the deadliest malignancy, with limited effective and long-term therapeutic options. Immunotherapy has revolutionized the therapeutic landscape of lung cancer. However, not everyone with lung cancer responds to immunotherapy, while, inpatients who temporarily derive clinical benefit, resistance eventually develops. The host microbiome has emerged as a pivotal player in cancer growth and progression. It has been implicated in the intricate connections between immune cells and tumor cells, ultimately augmenting immunotherapy efficacy in solid tumors, while simultaneously mitigating the immune-related adverse events associated with this type of treatment. Notably, lung cancer patients who obtain benefit from immunotherapy have been found to be colonized with specific bacterial populations, and it is this observation that the scientific community is trying to exploit, aspiring to improve lung cancer immunotherapy response rates. Delving deeper into the molecular mechanisms underpinning the effects of the microbiome on immunotherapy is an area that we should pay attention to if we want to utilize microbiome modulation in everyday clinical practice. Fecal microbiota transplantation, probiotics, targeted antibiotic interventions, and dietary modifications are among the strategies that are under investigation in clinical trials, with the ultimate endpoint of lengthening the life expectancy of lung cancer patients.

Lung cancer is the leading cause of cancer-related mortality worldwide, with the American Cancer Society estimating approximately 124,730 deaths from lung cancer in 2025

Ancient Greek physicians, including Hippocrates, documented skin conditions resembling herpes as early as 500 before common era (BCE), but it was not until the 1920s that Lowenstein successfully isolated the herpes virus from human lesions, significantly advancing our understanding of the infection

Pulmonary fibrosis (PF) is a severe, irreversible lung disease characterized by progressive scarring, with idiopathic pulmonary fibrosis (IPF) being the most prevalent form. IPF’s pathogenesis involves repetitive lung epithelial injury leading to fibroblast activation and excessive extracellular matrix (ECM) deposition. The prognosis for IPF is poor, with limited therapeutic options like nintedanib and pirfenidone offering only modest benefits. Emerging research highlights the dysregulation of the yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathway as a critical factor in PF. YAP and TAZ, components of the Hippo pathway, play significant roles in cell proliferation, differentiation, and fibrosis by modulating gene expression through interactions with TEA domain (TEAD) transcription factors. The aberrant activation of YAP/TAZ in lung tissue promotes fibroblast activation and ECM accumulation. Targeting the YAP/TAZ pathway offers a promising therapeutic avenue. Preclinical studies have identified potential treatments, such as trigonelline, dopamine receptor D1 (DRD1) agonists, and statins, which inhibit YAP/TAZ activity and demonstrate antifibrotic effects. These findings underscore the importance of YAP/TAZ in PF pathogenesis and the potential of novel therapies aimed at this pathway, suggesting a new direction for improving IPF treatment outcomes. Further research is needed to validate these approaches and translate them into clinical practice.