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RESEARCH PRODUCT

Actionable Molecular Targets in Cancer Liquid Biopsy

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The possibility to detect nucleic acid sequences in the bloodstream deriving from an underlying tumor process has disclosed a unique opportunity in medical oncology. Whether the nucleic acid material is leaked in the blood at any step of cancer development (circulating tumor DNA or ctDNA) or it is obtained from isolated circulating tumor cells (CTCs), the detection and analysis of the meaningful sequence defects harbored in instrumental molecular targets (which we call liquid biopsy) constitutes an invaluable tool toward leading the current oncology practice toward a less invasive and fully personalized diagnostic-therapeutic workflow. In spite of the current technical limitations that liquid biopsy still bears in terms of enrichment and/or isolation of the target test material (CTCs, ctDNA, etc.) from the bloodstream (widely discussed in the other chapters), current advancements in nanotechnologies as well as in pathway-driven biology knowledge of the cancer process now allow medical science to adopt universal pre-analytical and analytic methodologies. The key aspect that currently concerns the medical oncology field still remains what molecular targets should be pursued in the clinical practice (sequential monotherapies versus smart combinations) at the light of the experience accumulating on the mechanisms of acquired resistance to molecular monotherapies (even the most effective ones). While the previous chapters provide cancer-specific perspective on the use of liquid biopsy, in this chapter we summarize the general evidences toward the use of individual and combined molecular targets in liquid biopsy focusing on the experimental work conducted in the last few years toward validating this tool in parallel with the target validation data obtained by cancer genome wide studies. Even though the chapter is not meant to provide an exhaustive source for the constantly growing validated molecular targets in liquid biopsy testing (covered by other authors and through the references herein), it aims to provide an overview of the currently tested molecular targets shown to be linked to the evolution of the disease while focusing on the diagnostic and/or therapeutic monitoring value of the test.