Surmounting Chemotherapy and Radioresistance in Chondrosarcoma: Molecular Mechanisms and Therapeutic Targets

Figure 1

An overview of how chondrosarcoma cells evade the cytotoxic effects of chemotherapy and radiation. In normal cells, radiation and chemotherapy cause cell death by inducing genetic damage either directly, or in the case of radiation, through a reactive oxygen species (ROS) intermediate. For example, the drug doxorubicin intercalates with DNA, preventing replication, while ROS cause strand breaks. This damage is sensed by the cell, and then through the actions of tumor suppressor proteins such as p16 or p53 and the proapoptotic proteins including Bax, Bak, and Bim, the cell undergoes apoptosis, becomes senescent, or necroses. The chondrosarcoma cell’s main defense against chemotherapeutic agents is P-glycoprotein, a membrane-bound pump that extrudes small, hydrophobic molecules from within the cell [10]. The action of P-glycoprotein can lower intracellular concentrations of chemotherapeutic agents beyond a point at which they exact their cytotoxic effects. Though radiation treatment still induces genetic damage in chondrosarcoma cells, several mutations allow them to survive. These mutations include inactivation of the gene encoding the important tumor suppressor p16 via methylation or deletion [11], and upregulation of the antiapoptotic proteins Bcl-2 and XIAP [12]. Figure adapted from Motifolio Cell and Nucleic Acid Toolkit.