Stress granule formation for increasing the efficiency of chemotherapy

Although chemotherapies are widely applied, their therapeutic potential against cancer cells can be dissatisfactory due to the resistance and the heterogeneity of tumors. Therefore, combinational therapy based on chemotherapy along with another compound, is a trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with less side effects to normal tissues. Some chemotherapies have been shown to induce the formation cytoplasmic structures called “stress granules”. Under stress conditions these granules contain mRNAs stalled during translation and many RNA-binding proteins. The roles of stress granules in cancer treatment have aroused great interest. In our study we are investigating the role of stress granule formation in cancer cells under chemotherapeutic stress. We chose to focus on chemotherapies that produce a robust, dose- and time-dependent SG response in various cancer cell lines. We have identified compounds that increase stress granule formation during the chemotoxic stress, and show that the combination of chemotherapy with these compounds increases the susceptibility of cancer cells to the chemotherapeutic agents, leading to apoptosis. We foresee the upregulation of stress granules as a means for reducing chemotherapy levels while increasing the effectivity of the treatment, and ultimately elevating the rates of cancer cell death.