In conclusion, we showed that (i) ABCG1 was robustly expressed in the metastatic aggregative cells, in tumors derived from them, and in some types of clinical cancer correlated with poor prognosis of patients; (ii) depletion of the ABCG1 pump triggered the autocrine accumulation of EVs and cancer cell death in tumoroids, indicating a novel therapeutic strategy by which redundant and toxic substances may be accumulated in tumors by ABCG1-depletion, leading to their regression. Here, ABCG1 is linked to cancer.