Hyperthermia has been shown to have promising antitumor effects for various types of malignant tumors. It is one of the most potent adjuvant cancer therapy when combined with radiotherapy and chemotherapy. The range of hyperthermia temperature (40-45 ℃) induces cell killing depending on the temperature and the period of treatment. Although the kinetics of cell inactivation by heat using clonogenic assay have been well studied, the molecular mechanism of heat-induced cell death is still unclear. Till now only two distinct forms of cell death, apoptosis and necrosis, induced by hyperthermia can be recognized morphologically. However, in the current classification on cell death twelve types of cell death have been described. The objective of this review is to overview heat-induced cell death based on the recent classification, summarize each of cell death type, evaluate clinical significance, and discuss future directions of the cell death research.

Heat shock protein 47 (HSP47) acts as a collagen-specific molecular chaperone that is required for maturation of various types of collagens and is mainly expressed in fibroblasts and myofibroblasts in which collagen is constitutively expressed, synthesized and secreted. HSP47 plays an essential role in the development of fibrotic diseases such as liver cirrhosis and chronic pancreatitis, suggesting that HSP47 is a candidate as an anti-fibrotic therapeutic target. It has been reported that HSP47 is expressed in several cancer cells and that the increased expression of HSP47 is associated with poor prognosis and high malignant grade of tumors. Besides the role of HSP47 as a collagen-specific chaperone, it has recently been unveiled that HSP47 directly interacts with the unfolded protein response transducer IRE1α and that its interaction regulates cell fate, growth and metastasis of cancer cells. This review focuses on the recent findings of the role of HSP47 in cancer cells and discusses the possibility of HSP47 as a therapeutic target for cancer therapy.