Book excerpt: Traditional cancer diagnosis relies on tissue biopsy, blood testing as well as medical imaging. By the detection moment, in most cases the tumor size may reach several millimeters and the risk of distant metastasis is unavoidable. Even, following drug treatment, there is no accurate and timely way to follow up the success of treatment. New reliable tumor-specific biomarkers/tools that allow non-invasive early cancer detection as well as monitoring of anti-cancer therapeutic regime is highly demanded. To tackle limitations of traditional cancer management, liquid biopsy has emerged which screen bodily fluids using ultrasensitive biosensing systems capable of simultaneous capturing and studying horizontal gene transfer (HGT) materials including circulating tumor cells (CTCs), exosomes, cell-free DNA, and apoptotic bodies. These are messengers and/or delivery systems by which tumor cells are communicating as well as transforming/sharing new phenotypes with each other resulting in drug resistance, distant metastatic outbreaks, and cancer recurrence. Acting as next-generation prognostic and therapeutic tools call for understanding the molecular mechanisms by which HGT works to tran