Alhazza Abdulelah, Oyegbesan Adenike, Bousoik Emira, Montazeri Aliabadi Hamidreza
Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, #211, 9401 Jeronimo Road, Irvine, CA 92618, USA.
Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 76313, Saudi Arabia.
Pharmaceuticals (Basel). 2025 Jun 14;18(6):895. doi: 10.3390/ph18060895.
After the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent resistance (also known as primary resistance) is a result of heterogeneity in cancer cells where a subpopulation of the cells do not show a favorable initial response to the drug, while acquired resistance (or secondary resistance), as the name suggests, is developed after repeated treatments due to the plasticity of cancer cells. Despite the introduction of a variety of molecularly targeted drugs to clinical practice, chemotherapy is still at the forefront of the battle against cancer. In this manuscript, we review the major mechanisms involved in MDR and resistance against different categories of molecularly targeted drugs separately, and review some of the strategies studied to overcome the resistance against cancer therapy. While MDR mechanisms have been reviewed previously, the molecular mechanisms of resistance to the latest generations of anticancer drugs are rarely reviewed as a group, and the connection between the two categories of resistance is often missing in this type of publication. Our aim is to illustrate a comprehensive picture of what the landscape of cancer treatment is today with respect to resistance. While this picture seems bleak, and it is the common belief that resistance is inevitable, understanding the mechanisms involved could potentially lead to more efficient approaches to overcoming this so far unbeatable obstacle.
在针对细胞毒性化疗的多药耐药（MDR）时代之后，对新开发的分子靶向药物产生耐药性似乎也不可避免。虽然对这两类抗癌药物产生耐药性的机制不同，但原理相似：固有耐药性（也称为原发性耐药）是癌细胞异质性的结果，其中一部分细胞亚群对药物没有良好的初始反应，而获得性耐药（或继发性耐药），顾名思义，是由于癌细胞的可塑性在反复治疗后产生的。尽管多种分子靶向药物已引入临床实践，但化疗仍处于抗癌斗争的前沿。在本手稿中，我们分别回顾了MDR以及对不同类别分子靶向药物产生耐药性所涉及的主要机制，并回顾了一些为克服癌症治疗耐药性而研究的策略。虽然之前已经对MDR机制进行了综述，但很少将对最新一代抗癌药物产生耐药性的分子机制作为一个整体进行综述，并且在这类出版物中常常缺少这两类耐药性之间的联系。我们的目的是全面描绘当今癌症治疗中耐药性的情况。虽然这幅图景看起来很黯淡，而且人们普遍认为耐药性是不可避免的，但了解其中涉及的机制可能会带来更有效的方法来克服这一迄今为止无法战胜的障碍。
