Alcohol-induced extracellular vesicle signatures: Exploring liquid biopsy biomarkers for early cancer detection and prognosis

Alcohol intake is a significant causative factor of cancer, affecting liver, colorectal, oral/esophageal, and breast cancers. The toxicity of alcohol is due to the breakdown to acetaldehyde that damages the DNA, interferes with metabolism, and generates oxidative stress. Such alterations undermine the immune system, disrupt the surrounding tissue environment, and create the conditions for cancer development. Extracellular vesicles (EVss), small particles released by cells, are a relatively recent development as important mediators of the process in recent years. EVss are also released more and are augmented with microRNAs, mitochondrial DNA, proteins, lipids and metabolites under alcohol exposure. Signals contained in these vesicles propagate injury, cause inflammation, induce fibrosis, favor the development of new blood vessels, and facilitate the survival and proliferation of cancer cells. Notably, EVss has been observed in blood, saliva and other body fluids, which means that they can be used as non-invasive tools of non-liquid biopsy. They are not only indicators of tissue injury, but also they actively mediate cancer biology. The presented manuscript is a thorough review of alcohol-associated EV patterns in various cancers and highlights how they can be used as a biomarker in the early diagnosis, prognosis, and treatment response. EV-based markers have proven to be more sensitive and specific as compared to traditional blood tests, including AFP and CEA especially in the detection of cancer in the early stage or predicting resistance to treatment. The present literature provides a summary of alcohol-induced EVs profiles in various cancers, making them dynamic effectors of carcinogenesis as well as biomarkers with clinical relevance, but also multi-omic EVs profiles is the most appropriate compared to the conventional markers of diagnostic/prognostic markers. The priorities in the clinical translation of EVs to the clinical setting are seen in the need to come up with unit protocols that can be used to isolate and analyze EVs and develop alcohol-specific patient cohorts that can reflect genetic and lifestyle differences that affect the performance of biomarkers. To pass regulatory validation and use the multi-omic EVs in practice, it will be necessary to validate them in large, well-characterised populations. The combination of these strategies makes alcohol-induced EVs signatures some of the most effective precision oncology and personalised cancer treatment tools.