Basic Research and Preclinical Evaluation of Photodynamic Therapy (PDT) for Malignant Brain Tumors to Improve Further Clinical Effectiveness

E. Ishikawa, H. Kohzuki, T. Tsurubuchi, A. Matsumura
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Abstract

The main tumor killing mechanism of photodynamic therapy (PDT) is apoptosis and necrosis of tumor cells after generation of singlet oxygen species and this effect is mainly dependent on the depth of laser irradiation penetration. PDT using talaporfin sodium as a photosensitizer has already been applied clinically for high-grade glioma treatment and improvement of its further therapeutic effect is highly desired. Recently, basic research and preclinical evaluation of PDT to improve its effect while minimizing surrounding normal tissue damage has been performed, since simply raising laser power to improve PDT effect is not realistic in view of damage to surrounding normal tissue. The main countermeasure might be the increase in accumulation of already known photosensitizers in tumor tissue. However, the search for mechanisms of tumor-specific accumulation of the photosensitizers and their interactions with key molecules of tumor cells is still underway. Using next generation photosensitizers and combination with immunotherapy, as well as increasing the tumor accumulation of existing photosensitizers, are important issues regarding basic research on and preclinical evaluation of PDT, and application of such new findings will result in the increase of the clinical role of PDT.
光动力疗法(PDT)治疗恶性脑肿瘤的基础研究及临床前评价以进一步提高临床疗效
光动力疗法(PDT)的主要杀伤机制是单线态氧生成后肿瘤细胞的凋亡和坏死,这种作用主要取决于激光照射穿透的深度。以他拉波芬钠为光敏剂的PDT已在临床上应用于高级别胶质瘤的治疗,其进一步的治疗效果有待进一步提高。鉴于PDT对周围正常组织的损伤,单纯提高激光功率来提高PDT的效果是不现实的,为了提高PDT的效果,同时尽量减少对周围正常组织的损伤,目前已经开展了PDT的基础研究和临床前评估。主要的对策可能是增加已知光敏剂在肿瘤组织中的积累。然而,对肿瘤特异性光敏剂积累及其与肿瘤细胞关键分子相互作用机制的研究仍在进行中。使用新一代光敏剂并联合免疫治疗,增加现有光敏剂的肿瘤蓄积,是PDT基础研究和临床前评价的重要问题,这些新发现的应用将增加PDT的临床作用。
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