Overcoming multidrug resistance represents a major challenge for cancer treatment. In the search for new chemotherapeutics to treat malignant diseases, drug repurposing gained a tremendous interest during the past years. Repositioning candidates have often emerged through several stages of clinical drug development, and may even be marketed, thus attracting the attention and interest of pharmaceutical companies as well as regulatory agencies. Typically, drug repositioning has been serendipitous, using undesired side effects of small molecule drugs to exploit new disease indications. As bioinformatics gain increasing popularity as an integral component of drug discovery, more rational approaches are needed. Herein, we show some practical examples of in silico approaches such as pharmacophore modelling, as well as pharmacophore- and docking-based virtual screening for a fast and cost-effective repurposing of small molecule drugs against multidrug resistant cancers. We provide a timely and comprehensive overview of compounds with considerable potential to be repositioned for cancer therapeutics. These drugs are from diverse chemotherapeutic classes. We emphasize the scope and limitations of anthelmintics, antibiotics, antifungals, antivirals, antimalarials, antihypertensives, psychopharmaceuticals and antidiabetics that have shown extensive immunomodulatory, antiproliferative, pro-apoptotic, and antimetastatic potential. These drugs, either used alone or in combination with existing anticancer chemotherapeutics, represent strong candidates to prevent or overcome drug resistance. We particularly focus on outcomes and future perspectives of drug repositioning for the treatment of multidrug resistant tumors and discuss current possibilities and limitations of preclinical and clinical investigations.

克服多药耐药性是癌症治疗的主要挑战。在寻找用于治疗恶性疾病的新化学疗法中，药物的重新使用在过去几年中引起了极大的兴趣。重新定位的候选人通常在临床药物开发的多个阶段出现，甚至可能上市，从而引起了制药公司和监管机构的关注和兴趣。通常，药物重新定位是偶然的，使用小分子药物的不良副作用来开发新的疾病适应症。随着生物信息学作为药物发现不可或缺的组成部分而日益普及，需要更合理的方法。这里，我们展示一些计算机模拟的实际例子诸如药效基团建模以及基于药效基团和对接的虚拟筛选等方法，可快速，经济高效地重新利用小分子药物对抗多药耐药性癌症。我们提供了及时而全面的概述，这些化合物具有巨大的潜力，可以重新定位用于癌症治疗。这些药物来自不同的化学治疗类别。我们强调驱虫药，抗生素，抗真菌药，抗病毒药，抗疟疾药，抗高血压药，心理药物和抗糖尿病药的范围和局限性，这些药物已显示出广泛的免疫调节，抗增殖，促凋亡和抗转移潜力。这些药物可以单独使用，也可以与现有的抗癌化学疗法联合使用，可以预防或克服耐药性。