Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York; University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York.
University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York.
J Surg Res. 2021 Jul;263:245-250. doi: 10.1016/j.jss.2020.12.067. Epub 2021 Mar 11.
Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration-approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice.
Human non-small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT.
Porfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point.
PS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.
肺癌是美国癌症死亡的最大原因，需要不断改进当前的治疗技术。光动力疗法（PDT）涉及光敏剂、光和氧的相互作用。由此产生的活性氧物质的释放导致肿瘤坏死。它已被用作肺癌缓解的内镜技术。卟啉钠（Photofrin）是唯一获得美国食品和药物管理局批准用于 PDT 的光敏剂，但穿透深度有限，并产生持久的皮肤光毒性。正在开发多种新型光敏剂，包括 PS785。在小鼠中，将 PS785 的疗效与卟啉钠进行了比较，用于治疗人肺癌异种移植物。
在严重联合免疫缺陷小鼠中建立人非小细胞肺癌（NSCLC）异种移植物，并将其分为小（3-5mm）和大肿瘤（6-10mm）。PS785 或卟啉钠静脉给药，注射后 24、48 或 72 小时进行 PDT。主要终点是 PDT 后肿瘤复发的延迟。
当小肿瘤在 24 和 48 小时治疗时，卟啉钠和 PS785 产生的 PDT 后肿瘤复发延迟具有统计学上的相似性。在 72 小时时，PS785 在小肿瘤中表现更好。然而，对于大肿瘤，PS785 在任何时间点都没有延迟肿瘤复发。
PS785 和卟啉钠能够有效地治疗 NSCLC 至≤5mm 的深度。然而，卟啉钠在治疗 6-10mm 深度的 NSCLC 肿瘤方面更有效。需要进一步努力开发能够促进更大肿瘤 PDT 的光敏剂。
