Additionally, it allows for the longitudinal evaluation of cancer evolution. Liquid biopsy often represents a rapid and non-invasive alternative to tissue biopsy. urine, saliva, ascites, pleural effusion or cerebrospinal fluid). To overcome these limitations, in recent years there has been an increasing development of liquid biopsy, defined as the sampling and analysis of non-solid biological tissue, such as blood and most other bodily fluids (e.g. However, it has a number of limitations: it is an invasive method it is not always feasible or repeatable it provides information limited to a single point in space and time, therefore failing to capture the complex tumor heterogeneity. Tissue biopsy is the most widely used method for categorizing tumors and detecting biomarkers. There is growing recognition that immunoediting, the process whereby the immune system can both counteract and promote tumor development, contributes to cancer heterogeneity and represents a potential source of biomarkers. In particular, the dynamic interplay between cancer and immune cells has become an issue of great interest. The TME includes proliferating tumor cells, the tumor stroma, surrounding blood vessels, and immune cells. The tumor microenvironment (TME), defined as the complex ecosystem in which cancer cells interact with non-cancerous cells, represents an additional source of intra-tumor heterogeneity. It exists at multiple levels and may be present within different tumor regions or between primary cancer and metastases (spatial heterogeneity), or during the course of disease progression (temporal heterogeneity). Tumor heterogeneity refers to the coexistence of different biological, morphological, phenotypic and genotypic profiles, between tumors (inter-tumor heterogeneity) and within tumors (intra-tumor heterogeneity). In many cases, however, these biomarkers are not uniformly present in all cancer cells, and such heterogeneity might hinder the therapeutic efficacy of tailored therapies. The use and efficacy of such tailored therapies, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors, often relies on the presence of specific tumor biomarkers, such as activating gene mutations or expression levels of specific proteins. In the last decades, advances in precision medicine have radically changed the therapeutic scenario in medical oncology. We specifically focused on its role as a tool to capture tumor heterogeneity in metastatic cancer patients. In this review, we discuss the current and possibly future applications of blood-based liquid biopsy in oncology, its advantages and its limitations in clinical practice. A blood-based liquid biopsy can capture circulating tumor cells and leukocytes, as well as circulating tumor-derived nucleic acids. Samples can be obtained from blood and most other bodily fluids. Liquid biopsy is the sampling and analysis of non-solid biological tissue often through rapid and non-invasive methods, which allows the assessment in real-time of the evolving landscape of cancer. Tumor heterogeneity represents indeed one of the main causes of therapeutic failure, and its decoding remains a major ongoing challenge in the field. ![]() Due to the dynamic nature of cancer, very often these predictive biomarkers are not uniformly present in all cancer cells. In a large number of cancer types, treatment selection depends on the presence of specific tumor biomarkers.
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