Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcala, Alcala de Henares, Madrid, Spain.
iMed.ULisboa - Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, Lisbon 1649-003, Portugal.
Curr Pharm Des. 2018;24(36):4312-4333. doi: 10.2174/1381612825666190110162529.
The exponential growth of cancer cases worldwide together with recent advances concerning the pathophysiological mechanisms of the disease at the molecular level led to a paradigm shift in chemotherapy, from monotherapy to targeted drug combination regimens. However, adverse effects and the emergence of multidrug resistance (MDR) limit the effectiveness of these therapies. In this context, hybrid combinations mixing anticancer drugs and bioactive phytochemical components from medicinal plants, or even plant extracts, that can act synergistically on multiple targets and signaling pathways represent a promising approach with the potential to expand the current therapeutic arsenal. This review aims to provide a synopsis on anticancer hybrid combinations based on their multi-target mechanisms and synergistic effects from an extensive literature search focusing mainly on publications from the last ten years. In most of these combinations, the phytochemical component was shown to enhance the anticancer activity of the chemotherapeutic agent and to sensitize chemoresistant tumors in several types of cancer. Hybrid combinations, due to synergistic interactions, are also associated with less severe adverse events since lower doses can be used to achieve the same therapeutic effect. Further preclinical and clinical studies are needed, as well as the development of an adequate regulatory framework, before hybrid combination therapy can be translated into clinical practice.
全球癌症病例呈指数级增长，加上近年来在分子水平上对疾病病理生理机制的研究进展，促使化疗从单一药物治疗向靶向药物联合治疗方案发生了范式转变。然而，不良反应和多药耐药（MDR）的出现限制了这些疗法的有效性。在这种情况下，混合组合将抗癌药物与来自药用植物的生物活性植物化学成分甚至植物提取物混合使用，这些组合可以针对多个靶点和信号通路协同作用，代表了一种有前途的方法，有可能扩大当前的治疗武器库。本综述旨在从广泛的文献检索中提供基于多靶点机制和协同作用的抗癌混合组合的概述，主要关注过去十年的出版物。在这些组合中的大多数中，植物化学成分被证明可以增强化疗药物的抗癌活性，并使多种类型癌症中的耐药肿瘤变得敏感。由于可以使用较低的剂量来达到相同的治疗效果，因此混合组合还与更严重的不良反应相关。在将混合组合疗法转化为临床实践之前，还需要进行更多的临床前和临床研究，并制定适当的监管框架。
