Fig. 11

Proposed mechanism of chemoresistance MDV-mediated. In chemosensitive cells, cisplatin uptake induces mitochondrial damage and generation of MDVs which are destined to MVBs and then degraded in lysosomes, or, alternatively, to a limited extent secreted. Under these conditions, cisplatin determines lysosomal membrane permeabilization (LMP) and cell death by apoptosis. In chemoresistant cells, mitochondria are dysfunctional and the cell responds to cisplatin increasing the number of MDVs. This cell is also characterized by a lysosomal deficit, and this condition determines massive secretion of MDVs outside the cells to propagate chemoresistance in the cancer microenvironment