Effect of Heating Prior to Gemcitabine Exposure on Therapeutic Outcomes in Combination Therapies

概要

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Using chemotherapy alone, it is difficult to cure patients with solid tumors. However, chemotherapy combined with heat treatment enhances cytotoxicity by improving drug delivery to tumor tissues, leading to improvements in the cure rate. Nuclear factor-kappa B (NF-κB) has been reported to be activated by chemotherapy in some cancer cell lines, and NF-κB activation is one mechanism through which tumors can become resistant to chemotherapy. Heat treatment-induced heat shock protein 70 (Hsp70) was reported to inhibit I kappa B (Iκ-B) kinase (IKK), resulting in the inhibition of NF-κB activation. In view of this observation, it appeared to be possible that activation of NF-κB in a pancreatic cell line might be inhibited by heat treatment, leading to an enhancement of gemcitabine-induced cytotoxicity. However, the timing of the heat treatment is also very important in producing chemosensitization when combined with chemotherapy. In this review, the timing of a heat treatment in relation to a gemcitabine treatments is discussed, along with the mechanisms leading to sensitization in combination therapy.
日本ハイパーサーミア学会の論文