Reduction of cellular cisplatin resistance by hyperthermia—a review

Abstract

Resistance to cisplatin (cDDP) is a major limitation to its clinical effectiveness. Review of literature data indicates that cDDP resistance is a multifactorial phenomenon. This provides an explanation why attempts to reverse or circumvent resistance using cDDP-analogues or combination therapy with modulators of specific resistance mechanisms have had limited success so far. It therefore provides a rationale to use hyperthermia, an agent with pleiotropic effects on cells, in trying to modulate cDDP resistance. In this review the effects of hyperthermia on cDDP cytotoxicity and resistance as well as underlying mechanisms are discussed. Hyperthermia is found to be a powerful modulator of cDDP cytotoxicity, both in sensitive and resistant cells. Relatively high heat doses (60 min 43 degrees C) seem to specifically interfere with cDDP resistance. The mechanism of interaction has not been fully elucidated so far, but seems to consist of multiple (simultaneous) effects on drug accumulation, adduct-formation and -repair. This may explain why hyperthermia seems to be so effective in increasing cDDP cytotoxicity, irrespective of the presence of resistance mechanisms. Therefore, the combination of hyperthermia and cDDP deserves further attention.

The role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer: A Review

“…Hyperthermia also reduces the mechanisms of cellular resistance to cisplatin. [28][29][30] It has been demonstrated that heat increases cisplatin accumulation in platinum resistant cell lines. In both platinum sensitive and platinum resistant cell lines both, it sensitizes the cells for cisplatin by mechanisms like increase accumulation in the cells, increased cisplatin and DNA adduct formation and decreased removal of these adducts from the cells.…”

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

“…Eventually, DNA damage increased while DNA repair decreased. Additionally, hyperthermia was reported to have a potential ability to avoid drug resistance [86,87] . In addition, it is also expected that elevated blood flow could result in a relative increase in anticancer drug concentration within the tumor.…”

Reduced endocytosis and altered lysosome function in cisplatin-resistant cell lines

“…Intrinsic or acquired resistance of tumour cells to CP undermines its clinical effectiveness (Niedner et al, 2001). Mechanisms of resistance include decreased drug accumulation (Shen et al, 2000), changes in DNA repair proficiency (Fink et al, 1998;Zhen et al, 1992;Chu, 1994;Lai et al, 1995;Johnson et al, 1996), metallothionein (MT II) (Kelly et al, 1988;Kondo et al, 1995), glutathione-related enzymes (Moscow and Cowan, 1988;Godwin et al, 1992;Zaman et al, 1995), stress response proteins (Shen et al, 1995;Hettinga et al, 1997), proto-oncogenes or apoptosis-related genes, and cancer susceptibility genes (Fanidi et al, 1993;Lowe et al, 1993;DeFeudis et al, 1996;Husain et al, 1998;Moorehead and Singh, 2000). Protein kinases (PKs) like PKA and PKC have also been associated with CP-resistance (CP-r) and use of their specific inhibitors has been demonstrated to increase CP cytotoxicity in resistant tumour cells (Gosland et al, 1996).…”