In this review, we summarize the molecular mechanisms of chemical inhibitors and small interference RNAs (siRNAs) specifically targeted against signaling factors involving in heat-induced signal transduction pathways for anti-apoptosis/cellular proliferation and DNA repair. Since there are still few reports of the chemical inhibitors and siRNAs with respect to sensitization to heat, the effective chemical inhibitors and siRNAs which block the signal transduction pathways are required from an aspect of fundamental research. We expect the attractive sensitizers described here to contribute to high curative efficiency in hyperthermic cancer therapy.

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Background : For the patients with unresectable pancreas cancer, improvement of quality of life (QOL) and prolongation of prognosis are most important proposition. The consecutive treatment with few side effects is required. For an unresectable pancreas cancer, we perform the hyperthermic therapy combined with low dose Gemcitabine Hydrochloride (GEM). In this study, we reviewed clinical significance of thermochemotherapy for unresectable pancreas cancer as tumor dormancy therapy.
Object and a method : For the 10 patients with unresectable pancreas cancer, we have performed thermochemotherapy. Hyperthermia was administerd once a week and GEM was simultaneously given during hyperthermia. The effect of thermo-chemotherapy was evaluated from tumor contraction effect, variation of tumor marker value, and clinical benefit (assessed by pain relief and Karnofsky Performance status (KPS)). The prognosis of these patients compared with the 11 patients received best supportive with unrespectable pancreas cancer (BSC group).
Results : The frequency of thermochemotherapy ranged from four sessions to 43 sessions (19.6 ± 12.1). As the antitumor effects, response rate was 10% and the decrease of a tumor marker was found in eight patients (80%). Responder in clinical benefit was recognized in six patients (60%). Median survival periods were 212 days of the patients in the TC group, and 140 days in the BSC group. The significant difference was accepted in both survival curves. Three out of 11 patients in the BSC and nine of 10 patients in the TC group could discharge from the hospital. Severe adverse reaction as grade 3 or 4 was not cncountcrcd.
Summary : The hyperthermic treatment combined with low dose GEM for the patients with unresectable pancreas cancer could be continued for a long term under the favor of few harmful toxicity, and which should bring about the favorable clinical benefit and the improvement of prognosis.

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Malignant pleural mesothelioma (MPM) is considered to carry very poor prognoses and reported surgical results revealed median survival time to be less than one year for UICC-stage I to III. Instead of surgery, we performed thermoradiotherapy combined with chemotherapy using platinum compounds into the pleural cavity for the treatment of this disease. We experienced 8 cases of UICC-stage I to III MPM and 3 of them got good response and survival time of more than 2 years, respectively (median survival time was 14.1 months). This treatment method might be well tolerated by the patient with good quality and quantity of life. Furthermore, the amount of the pleural effusion was controlled in most patients. As radical aggressive treatment carries considerable risk of mortality and morbidity, this organ-conserving trimodal therapy might be an alternative treatment modality.

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A female patient underwent a total ovario-hysterectomy for metastasis after a gastrectomy, and disseminated peritoneal metastasis was detected.
At another hospital, the patient was informed that chemotherapy would not be effective treatment ; as a result, she chose to undergo chemothermotherapy at Matsuyama West Hospital.
The patient responded to chemothermotherapy, and FDG-PET images showed the disappearance of the disseminated tumor. The quality of life (QOL) for this patient improved remarkably, and she survived for more than 300 days after the treatment.

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