###### Abstract  
Tumor-secreted extracellular vesicles (EVs) are the main mediators of cell-cell communication, permitting cells to exchange proteins, lipids, and metabolites in varying physiological and pathological conditions. They contain signature tumor-derived molecules that reflect the intracellular status of their cell of origin. Recent studies have shown that tumor cell-derived EVs can aid in cancer metastasis through the modulation of the tumor microenvironment, suppression of the immune system, pre-metastatic niche formation, and subsequent metastasis. EVs can easily be isolated from a variety of biological fluids, and their content makes them useful biomarkers for the diagnosis, prognostic, monitorization of cancer progression, and response to treatment. This review aims to explore the biomarkers of cancer cell-derived EVs obtained from liquid biopsies, in order to understand cancer progression and metastatic evolution for early diagnosis and precision therapy.  
extracellular vesicles; liquid biopsy; biomarkers; tumor progression; metastasis +
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to their size and biogenesis, EVs are classified into the following groups: exosomes, microvesicles, and apoptotic bodies. Exosomes (30-120 nm in diameter) are initially generated inside of multivesicular bodies (MVBs), existing as intraluminal vesicles (ILVs). When these MVBs fuse with the cell membrane, vesicles are released into the extracellular space, where they become known as \"exosomes\" [10]. In contrast to exosomes, microvesicles are formed by a characteristic \"outward blebbing\" of the plasma membrane, producing a class of heterogeneous vesicles of larger size (100 nm-1 \(\upmu\)m in diameter). The formation of microvesicles appears to occur selectively in lipid-rich membrane microdomains (e.g., in lipid rafts) [11]. These vesicles are often given other names, including endosomes, shedding vesicles, or oncogenes (in the case of cancer cells) [12]. Apoptotic bodies (1-5 \(\upmu\)m in diameter) are released during the last steps of apoptosis through formation of membrane protrusions, such as microtubule spikes, apoptopodia, and beaded-apoptopodia. Although these classifications have been widely used in the literature, it is advised to use this nomenclature sparingly. This is due to the fact that most techniques currently used only allow the separation of small EVs from large EVs [12]. Consequently, the International Society for Extracellular Vesicles (ISEV) recommends using terms for EV subtypes, such as size, density, instead of using terms such as \"exosomes\" or \"microvesicles\", unless there is certainty of their biogenesis [13].  
Liquid biopsies are a rich source of EVs and are typically obtained using minimally invasive medical procedures that allow sampling from healthy controls, and therefore allows the detection of minimal residual disease (MRD) or recurrence and tracking of tumor evolution. It has been demonstrated that cancer cell-associated EVs carry the signatures of proteins, lipids, metabolites, and RNA of the tumor cell of origin [9]. Additionally, cancer-derived EVs are important players in cancer progression, being able to facilitate intercellular communication with cells near and far away (e.g., stromal cells), promoting the formation of pre-metastatic niches. EVs are involved in different stages of tumorigenesis and metastasis by increasing angiogenesis and remodeling the extracellular matrix. This activity allows cells to escape from immune system recognition and induces resistance to various cancer therapies [14; 15]. For this reason, molecular profiling of EVs can help us understand the behavior of the cancer, in order to obtain an early diagnosis and develop targeted therapies.  
In this review, we aim to cover the fields' most recent findings in proteomic, lipidomic, and metabolomic studies in EVs. We will highlight the best practices for identification of tumor biomarkers by cancer cell-derived EVs, placing an emphasis on the hallmarks of cancer, promotion of invasion, and metastasis