在过去的二十年里，阐明了致癌的基因缺陷，产生了大量新型的靶向癌症药物。虽然这些药物最初可能非常有效，但是单一治疗药物存在抵抗性仍是一个主要挑战。联合用药可以避免抵抗性，但是可测试的药物组合数量远远超过了临床实验所能承受的范围，无论是财务方面还是在患者可得性方面。基于深刻理解治疗抵抗相关的分子机制，理性地组合药物在癌症治疗中具有潜在的强大作用。在这里，我们讨论了靶向治疗的抵抗机制以及如何鉴定有效的联合用药来对抗抗药性。这也考虑到了开发这些组合药物的临床挑战和未来的展望。 © 2022 Springer Nature Limited.

Over the past two decades, elucidation of the genetic defects that underlie cancer has resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be highly effective, resistance to single-agent therapies remains a major challenge. Combining drugs can help avoid resistance, but the number of possible drug combinations vastly exceeds what can be tested clinically, both financially and in terms of patient availability. Rational drug combinations based on a deep understanding of the underlying molecular mechanisms associated with therapy resistance are potentially powerful in the treatment of cancer. Here, we discuss the mechanisms of resistance to targeted therapies and how effective drug combinations can be identified to combat resistance. The challenges in clinically developing these combinations and future perspectives are considered.© 2022. Springer Nature Limited.