Department of Internal Medicine, Oncology Unit, Hippokrateio Hospital, University of Athens, Athens, Greece.
Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, 35340, Izmir, Turkey.
Clin Exp Metastasis. 2018 Apr;35(4):309-318. doi: 10.1007/s10585-018-9903-0. Epub 2018 May 24.
It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and recurrence. This phenomenon of acquired resistance to therapy, it is a major problem for totally efficient anticancer therapy. The failure to obtain an initial response reflects a form of intrinsic resistance. Specific cell membrane transporter proteins are implicated in intrinsic drug resistance by altering drug transport and pumping drugs out of the tumor cells. Moreover, the gradual acquisition of specific genetic and epigenetic abnormalities in cancer cells could contribute greatly to acquired drug resistance. A critical issue in the clinical setting, is that the problem of drug resistance appears to have a negative effect on also the new molecularly-targeted anticancer drugs. Several ongoing efforts are being made by the medical community aimed to the identification of such resistance mechanisms and the development of novel drugs that could overcome them. In this review, the major drug resistance mechanisms and strategies to overcome them are critically discussed, and also possible future directions are suggested.
人们普遍认为，近年来抗癌药物的进展显著提高了癌症患者的无病生存率和生活质量。然而，在许多情况下，最初对治疗的有利反应随后会发生变化，从而导致癌症复发和转移。这种对治疗的获得性耐药现象是完全有效的抗癌治疗的一个主要问题。未能获得初始反应反映了一种内在的耐药形式。特定的细胞膜转运蛋白通过改变药物转运并将药物泵出肿瘤细胞，从而导致内在药物耐药。此外，癌细胞逐渐获得特定的遗传和表观遗传异常，可能极大地促成获得性耐药。在临床环境中一个关键问题是，耐药问题似乎对新型的分子靶向抗癌药物也有负面影响。医学界正在进行几项努力，旨在确定这些耐药机制，并开发克服这些机制的新药。在这篇综述中，批判性地讨论了主要的耐药机制和克服它们的策略，并提出了可能的未来方向。
