Papanagnou Panagiota, Papadopoulos Georgios E, Stivarou Theodora, Pappas Anastasios
Department of Urology, Agios Savvas Cancer Hospital, Athens 11522, Greece,
Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41500, Greece.
Onco Targets Ther. 2018 Dec 31;12:319-339. doi: 10.2147/OTT.S182685. eCollection 2019.
Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic use of octreotide is restricted primarily to the management of acromegaly and neuroendocrine tumors, both of which are rare medical conditions. Similarly, chloroquine is used mainly for the treatment of malaria, which is designated as a rare disease in Western countries. This limited exploitation contradicts the experimental findings of numerous studies outlining the possible expansion of the use of octreotide to include the treatment of common human malignancies and the repositioning of chloroquine in oncology. Herein, we review the current knowledge on the antitumor function of these two agents stemming from preclinical or clinical experimentation. In addition, we present in silico evidence on octreotide potentially binding to multiple Wnt-pathway components. This will hopefully aid in the design of new efficacious anticancer therapeutic regimens with minimal toxicity, which represents an enormous unmet demand in oncology.
生物系统中的多效性及其靶向作用使许多药物可用于多种治疗目的。充分利用已上市药物的治疗特性将具有极大优势。在肿瘤学领域尤其如此，典型抗癌药物的无效性是一个常见问题，而新型抗癌药物的研发成本高昂且特别耗时。奥曲肽和氯喹是两种具有显著抗肿瘤活性的药物。然而，目前奥曲肽的治疗用途主要限于肢端肥大症和神经内分泌肿瘤的管理，这两种都是罕见病症。同样，氯喹主要用于治疗疟疾，在西方国家这被认定为罕见疾病。这种有限的应用与众多研究的实验结果相矛盾，这些研究概述了奥曲肽可能扩大应用范围以包括治疗常见人类恶性肿瘤以及氯喹在肿瘤学中的重新定位。在此，我们综述了来自临床前或临床实验的关于这两种药物抗肿瘤功能的现有知识。此外，我们展示了奥曲肽可能与多种Wnt信号通路成分结合的计算机模拟证据。这有望有助于设计出毒性最小的新型有效抗癌治疗方案，这代表了肿瘤学中一个巨大的未满足需求。
