Exosomes from drug-resistant cells transfer oncogenic miR to sensitive cells and activate the PI3K/Akt pathway by negatively regulating the expression of the downstream target phosphatase and tensin homolog (PTEN), which induces VEGFA-mediated angiogenesis and increases microvessel density in the TME, mediating the multi-drug resistance of HCC (5-FU, OXA, GEM, and Sorafenib) (118). The gene discussed is AKT1; the disease is hepatocellular carcinoma.