抗癌药物的开发有望为癌症患者提供长期或至少短期的生存益处。不幸的是，药物治疗往往会引发癌细胞的恶性生物学和临床行为，这不仅与特定药物耐药性的演变有关，而且还与癌细胞增殖和转移能力的增强有关。因此，在某些情况下，药物治疗被怀疑会损害接受治疗的患者的长期生存。这种矛盾的治疗效果可谓“以毒止渴”，不顾后果只求暂时缓解。了解肿瘤对药物引起的应激反应以维持生存能力的潜在机制对于开发合理的靶向方法至关重要，从而优化癌症患者的生存。在这篇综述中，我们描述了抗癌药物的矛盾副作用，特别是癌细胞在遇到药物治疗时如何完成耐药性进化、增强增殖、逃避免疫监视和有效转移。我们还描述了一种可能减少这种矛盾效应的综合治疗框架，包括四种主要策略：（1）针对内源性应激反应途径，（2）针对癌细胞的新特性，（3）适应性治疗——利用癌症的亚克隆竞争细胞，(4) 靶向肿瘤微环境。版权所有 © 2023。由 Elsevier Ltd 出版。

Anticancer drugs have been developed with expectations to provide long-term or at least short-term survival benefits for patients with cancer. Unfortunately, drug therapy tends to provoke malignant biological and clinical behaviours of cancer cells relating not only to the evolution of resistance to specific drugs but also to the enhancement of their proliferation and metastasis abilities. Thus, drug therapy is suspected to impair long-term survival in treated patients under certain circumstances. The paradoxical therapeutic effects could be described as 'quenching thirst with poison', where temporary relief is sought regardless of the consequences. Understanding the underlying mechanisms by which tumours react on drug-induced stress to maintain viability is crucial to develop rational targeting approaches which may optimize survival in patients with cancer. In this review, we describe the paradoxical adverse effects of anticancer drugs, in particular how cancer cells complete resistance evolution, enhance proliferation, escape from immune surveillance and metastasize efficiently when encountered with drug therapy. We also describe an integrative therapeutic framework that may diminish such paradoxical effects, consisting of four main strategies: (1) targeting endogenous stress response pathways, (2) targeting new identities of cancer cells, (3) adaptive therapy- exploiting subclonal competition of cancer cells, and (4) targeting tumour microenvironment.Copyright © 2023. Published by Elsevier Ltd.