Division of Pharmaceutical, Administrative, and Social Sciences Duquesne University Pittsburgh PA USA.
Indiana University School of Medicine Indianapolis IN USA.
Pharmacol Res Perspect. 2018 Jul 5;6(4):e00417. doi: 10.1002/prp2.417. eCollection 2018 Jul.
Breast cancer treatment using a single drug is associated with a high failure rate due, in part, to the heterogeneity of drug response within individuals, nonspecific target action, drug toxicity, and/or development of resistance. Use of dual-drug therapies, including drug conjugates, may help overcome some of these roadblocks by more selective targeting of the cancer cell and by acting at multiple drug targets rather than one. Drug-conjugate approaches include linking drugs to antibodies (antibody-drug conjugates), radionuclides (radioimmunoconjugates), nanoparticles (nanoparticle-drug conjugates), or to other drugs (drug-drug conjugates). Although all of these conjugates might be designed as effective treatments against breast cancer, the focus of this review will be on drug-drug conjugates because of the increase in versatility of these types of drugs with respect to mode of action at the level of the cancer cell either by creating a novel pharmacophore or by increasing the potency and/or efficacy of the drugs' effects at their respective molecular targets. The development, synthesis, and pharmacological characteristics of drug-drug conjugates will be discussed in the context of breast cancer with the hope of enhancing drug efficacy and reducing toxicities to improve patient quality of life.
由于药物反应的个体内异质性、非特异性靶标作用、药物毒性和/或耐药性的发展等部分原因,单一药物治疗乳腺癌的成功率较低。使用双药物疗法,包括药物偶联物,可以通过更有针对性地靶向癌细胞,并通过作用于多个药物靶点而不是一个靶点来克服其中一些障碍。药物偶联物的方法包括将药物与抗体(抗体-药物偶联物)、放射性核素(放射性免疫偶联物)、纳米颗粒(纳米颗粒-药物偶联物)或其他药物(药物-药物偶联物)连接起来。尽管所有这些偶联物都可以设计为针对乳腺癌的有效治疗方法,但本综述的重点将放在药物-药物偶联物上,因为这些药物的多功能性有所增加,在癌细胞水平上的作用方式通过创建新的药效团,或者通过提高药物在各自分子靶标上的效力和/或疗效。将在乳腺癌的背景下讨论药物-药物偶联物的开发、合成和药理学特征,以期提高药物疗效并降低毒性,从而提高患者的生活质量。