Inhibiting induction of heat shock proteins as a strategy to enhance cancer therapy

Abstract

Cancer treatments that incorporate thermal therapy and some systemic therapies induce the production of heat shock or stress proteins. The induced heat shock proteins could lessen the effect of the therapy by inhibiting apoptotic signaling and by acting as molecular chaperones to prevent irreversible cellular damage. Strategies that prevent the induction of heat shock proteins would result in more apoptosis and necrosis, improving the cancer therapy. This paper briefly reviews cancer therapies that induce the stress response, and proposes strategies to reduce the stress response.

Global gene expression analyses reveal changes in biological processes after hyperthermia in a rat glioma model

“…Enhancement of tumor antigen processing by increase of extra-cellular Hsp70 and increased susceptibility of NK-cells mediated tumor cell lysis have been reported [13,[15][16][17]34]. The HSPs also have effects inside the cells where they act as chaperons and inhibit apoptosis [14,32,48]. Stimulation of the immune system by HSPs indicate HSPs as suitable agents for immunotherapy [13,49] while their stimulation of growth and apoptosis implies that HSPs could be targets of therapy [14].…”

“…The HSPs also have effects inside the cells where they act as chaperons and inhibit apoptosis [14,32,48]. Stimulation of the immune system by HSPs indicate HSPs as suitable agents for immunotherapy [13,49] while their stimulation of growth and apoptosis implies that HSPs could be targets of therapy [14]. DNAJB4 is a Hsp40 kD protein, recently postulated to be an inhibitor of invasion, metastasis and angiogenesis [50,51].…”

“…Protein denaturation and aggregation, proposed to be important for cytotoxicity, heat radiosensitization as well as thermotolerance, have also been reported [10]. Heat shock proteins (HSPs) play an important part in development of thermotolerance [10,14], but they also have a role in innate and adaptive immunity [13,[15][16][17]. HT is a strong challenge for the tumor cells, which may respond dually by signaling towards both survival and cell death [10].…”

Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy

“…HSPs function as chaperones within the cell and protect cells from thermal damage by stabilizing unfolded proteins to prevent aggregation. Although a lot remains to be elucidated regarding HSPs, such as their role in cancer and the immune response [ 136 , 137 , 138 ], the practical result is that cells develop thermotolerance, which may persist for 72 to 120 h [ 139 ]. Thus, HT is typically applied once or twice a week in the clinic, whereas RT is applied daily.…”

Hyperthermia-induced apoptosis in Tca8113 cells is inhibited by heat shock protein 27 through blocking phospholipid scramblase 3 phosphorylation

“…Development of cellular heat tolerance is related to production of heat shock proteins [25]. Suppression of heat shock protein expression may be a strategy for cancer treatment [26,27]. HSPs include multiple families, among which low molecular weight HSPs, such as Hsp27 (27 kD), are closely associated with tumour progression.…”