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Figure 2. Interplay between GPCRs and EVs during cancer development, highlighting their therapeutic potential. (I) Mutated or oncogenic GPCRs mediate abnormal signaling pathways that can affect protein sorting, leading to a change in EV cargo, or modulate tumor EV biogenesis and secretion, or a combination of the two. (II) EV-mediated functional horizontal transfer of GPCRs can propagate oncogenic signaling in the recipient cells. (III) Uptake of oncogenic EVs, either via endocytosis (c) or perhaps direct membrane fusion (d), can affect endogenously expressed GPCR signaling, contributing to cancer development. Additionally, GPCRs can modulate EV uptake, for example, via docking to the GPCR via its ligand (e). Thus, GPCRs pose an interesting point of interception to target tumor EV-mediated cancer development and progression. a: microvesicle secretion; b: exosome secretion; c: EV endocytosis; d: EV-plasma membrane fusion; e: GPCR-mediated EV docking. GPCR: G protein-coupled receptor; MVB: multivesicular body; EV: extracellular vesicle; EE: early endosome.