Pros, cons and future prospects of ALA-photodiagnosis, phototherapy and pharmacology in cancer therapy - A mini review

5-Aminolevulinic acid (ALA)-induced photodynamic therapy (ALA-PDT) has achieved remarkable research accomplishments over the past 30 years, yet its application in medical oncology still awaits clear recognition as a valid alternative therapeutic modality. It is well documented that topical ALA-PDT enables the treatment of multiple skin lesions simultaneously, and provides excellent cosmetic results with no acquired multi-drug resistance (MDR). Furthermore, upon disease recurrence the treatment can be repeated resulting in the same therapeutic efficacy. Additionally, in oncological surgery, ALA fluorescence-guided resection is a practical and simple method for visualizing intra-operative brain and urological tumors with millimeter accuracy. The urgent challenge is to direct future research of ALA-phototherapy and fluorescence diagnosis to the maturation of their medical status in oncology. Therefore, the future objectives are to amplify critical evidence-based results of ALA-PDT safety and efficacy and to validate its unique advantages over other technologies. Strong statistical PDT documentation and the positive predictive values of protoporphyrin IX (PpIX)-guided surgery will persuade the medical community to implement ALA-based therapeutics into standard clinical and surgical oncology practice. Research must address the phenomenon that no MDR develops as a consequence of PDT, since MDR is the major stumbling block in oncological therapeutics. A feasible goal should be to improve ALA administration protocols based on recent knowledge that preactivation of the enzyme porphobilinogen deaminase enhances PpIX accumulation in cancer cells and photodestruction. Moreover the recent introduction of multifunctional ALA prodrugs that maximize photosensitizer biosynthesis, targeting multiple sub-cellular targets, may increase PDT anti-cancer efficacy in additional disease settings. In conclusion, well-documented clinical results, new ALA delivery protocols, and novel multifunctional ALA prodrugs may advance ALA-PDT to becoming a front-line cancer therapy.