Kast Richard E, Skuli Nicolas, Sardi Iacopo, Capanni Felix, Hessling Martin, Frosina Guido, Kast Anton P, Karpel-Massler Georg, Halatsch Marc-Eric
IIAIGC Study Center, 22 Church Street, Burlington, VT 05401, USA.
Abramson Family Cancer Research Institute, University of Pennsylvania, Cancer Center, 438 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
Brain Sci. 2018 Nov 22;8(12):203. doi: 10.3390/brainsci8120203.
The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its preferential conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently-marketed drugs-the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat-that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.
CAALA（5-氨基乙酰丙酸复合增强）方案的制定旨在弥补目前5-氨基乙酰丙酸（5-ALA）在胶质母细胞瘤治疗中存在的一些不足。5-ALA已被批准在胶质母细胞瘤手术前使用，以更好地将肿瘤与脑组织区分开来。5-ALA还因其被胶质母细胞瘤细胞摄取并优先转化为原卟啉IX，而用于胶质母细胞瘤的术中光动力治疗。原卟啉IX在暴露于410nm或635nm光后具有细胞毒性。CAALA使用四种目前已上市的药物——抗生素环丙沙星、铁螯合剂去铁酮、抗代谢物5-氟尿嘧啶和黄嘌呤氧化酶抑制剂非布司他——所有这些药物都有证据表明能够增强5-ALA介导的术中胶质母细胞瘤边界划分以及原位胶质母细胞瘤细胞的光动力细胞毒性。在用人类胶质母细胞瘤细胞进行异种移植的活体小型猪身上测试完整CAALA方案的数据，将确定推进CAALA进入临床试验的安全性和潜在益处。
