In particular, they found that CSC-derived EVs (from oral cancer cell tumorspheres) are enriched with miR-21-5p, an important mediator in cisplatin resistance, [159,160] and a direct regulator of tumor suppressor genes, such as programmed cell death 4 (PDCD4) and PTEN. This evidence concerns the gene PDCD4 and lip and oral cavity carcinoma.