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Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far. They are detected in body fluids and conditioned culture media from living cells. EVs play a crucial role in communication between cells and organs, both locally and over long distances. They are recognized for their ability to transport endogenous RNA and proteins between cells, including messenger RNA (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, and several other biomolecules. This review explores the dual utilization of EVs, serving not only for diagnostic purposes but also as a platform for delivering therapeutic molecules to cells and tissues. Through an exploration of their composition, biogenesis, and selective cargo packaging, we elucidate the intricate mechanisms behind RNA transport between cells via EVs, highlighting their potential use for both diagnostic and therapeutic applications. Finally, it addresses challenges and outlines prospective directions for the clinical utilization of EVs., CC BY 4.0Corresponding author: Hadi ValadiE-mail address: hadi.valadi@gu.se (H. Valadi).This work has been supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx – Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and The Swedish Knowledge Foundation (KKS, Grant ID: 2020-0014).

Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far. They are detected in body fluids and conditioned culture media from living cells. EVs play a crucial role in communication between cells and organs, both locally and over long distances. They are recognized for their ability to transport endogenous RNA and proteins between cells, including messenger RNA (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, and several other biomolecules. This review explores the dual utilization of EVs, serving not only for diagnostic purposes but also as a platform for delivering therapeutic molecules to cells and tissues. Through an exploration of their composition, biogenesis, and selective cargo packaging, we elucidate the intricate mechanisms behind RNA transport between cells via EVs, highlighting their potential use for both diagnostic and therapeutic applications. Finally, it addresses challenges and outlines prospective directions for the clinical utilization of EVs., CC BY 4.0Corresponding author: Hadi ValadiE-mail address: hadi.valadi@gu.se (H. Valadi).This work has been supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx – Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and The Swedish Knowledge Foundation (KKS, Grant ID: 2020-0014).

Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far. They are detected in body fluids and conditioned culture media from living cells. EVs play a crucial role in communication between cells and organs, both locally and over long distances. They are recognized for their ability to transport endogenous RNA and proteins between cells, including messenger RNA (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, and several other biomolecules. This review explores the dual utilization of EVs, serving not only for diagnostic purposes but also as a platform for delivering therapeutic molecules to cells and tissues. Through an exploration of their composition, biogenesis, and selective cargo packaging, we elucidate the intricate mechanisms behind RNA transport between cells via EVs, highlighting their potential use for both diagnostic and therapeutic applications. Finally, it addresses challenges and outlines prospective directions for the clinical utilization of EVs., CC BY 4.0Corresponding author: Hadi ValadiE-mail address: hadi.valadi@gu.se (H. Valadi).This work has been supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx – Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and The Swedish Knowledge Foundation (KKS, Grant ID: 2020-0014).

Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far. They are detected in body fluids and conditioned culture media from living cells. EVs play a crucial role in communication between cells and organs, both locally and over long distances. They are recognized for their ability to transport endogenous RNA and proteins between cells, including messenger RNA (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, and several other biomolecules. This review explores the dual utilization of EVs, serving not only for diagnostic purposes but also as a platform for delivering therapeutic molecules to cells and tissues. Through an exploration of their composition, biogenesis, and selective cargo packaging, we elucidate the intricate mechanisms behind RNA transport between cells via EVs, highlighting their potential use for both diagnostic and therapeutic applications. Finally, it addresses challenges and outlines prospective directions for the clinical utilization of EVs., CC BY 4.0Corresponding author: Hadi ValadiE-mail address: hadi.valadi@gu.se (H. Valadi).This work has been supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx – Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and The Swedish Knowledge Foundation (KKS, Grant ID: 2020-0014).

Modern methods of molecular diagnostics and therapy have revolutionized the field of medicine in recent years by providing more precise and effective tools for detecting and treating diseases. This progress includes a growing exploration of the body's secreted vesicles, known as extracellular vesicles (EVs), for both diagnostic and therapeutic purposes. EVs are a heterogeneous population of lipid bilayer vesicles secreted by almost every cell type studied so far. They are detected in body fluids and conditioned culture media from living cells. EVs play a crucial role in communication between cells and organs, both locally and over long distances. They are recognized for their ability to transport endogenous RNA and proteins between cells, including messenger RNA (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, and several other biomolecules. This review explores the dual utilization of EVs, serving not only for diagnostic purposes but also as a platform for delivering therapeutic molecules to cells and tissues. Through an exploration of their composition, biogenesis, and selective cargo packaging, we elucidate the intricate mechanisms behind RNA transport between cells via EVs, highlighting their potential use for both diagnostic and therapeutic applications. Finally, it addresses challenges and outlines prospective directions for the clinical utilization of EVs., CC BY 4.0Corresponding author: Hadi ValadiE-mail address: hadi.valadi@gu.se (H. Valadi).This work has been supported by grants from the Swedish Foundation of Strategic Research (Stiftelsen för strategisk forskning: SSF) in the Industrial Research Centre, FoRmulaEx – Nucleotide Functional Drug Delivery (Grant ID: IRC15-0065), the Swedish research council (VR, Grant ID: 2020-01316), and The Swedish Knowledge Foundation (KKS, Grant ID: 2020-0014).

Background: Immune checkpoint-inhibitors (ICIs) are changing outcomes in different cancer settings, notably for patients with non-small-cell lung cancer (NSCLC). There are, however, still important gaps of evidence for clinical practice when using these novel treatments. In this study, we assessed physicians’ opinion and experience on challenges for clinical practice with ICIs monotherapy in NSCLC. Methods: A survey was conducted on experienced physicians treating patients with NSCLC with ICIs. Two rounds of pilot tests were carried out for validation among a group of experts. Topics under analysis were in relation to treatment of elderly populations, performance status, brain metastases, use of steroids or antibiotics, the effects of gut microbiome, autoimmune diseases, human immunodeficiency virus infection, solid organ transplants, use of anti-programmed cell death protein 1 versus anti-programmed death-ligand 1 drugs, atypical tumour responses, predictors of response, duration of treatment and a final open question on additional relevant challenges. Results: Two hundred and twenty-one answers were collected, including 106 (48%) valid answers from experts for final analysis (physicians who have treated at least 20 patients with NSCLC with ICIs). The vast majority agreed that the selected topics in this study are important challenges ahead and more evidence is needed. Moreover, predictors of response, treating brain metastasis, shorter duration of treatment, the effects of gut microbiome and concomitant use of steroids were voted the most important topics to be further addressed in prospective clinical research. Conclusions: This survey contributed to understanding which are the main challenges for clinical practice with ICIs monotherapy in NSCLC. It can also contribute to guide further clinical research, considering the opinions and experience of those who regularly treat NSCLC patients with ICIs., SCOPUS: ar.j, info:eu-repo/semantics/published