Deneka Alexander Y, Boumber Yanis, Beck Tim, Golemis Erica A
Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Department of Biochemistry, Kazan Federal University, 420000 Kazan, Russia.
Cancers (Basel). 2019 Sep 3;11(9):1297. doi: 10.3390/cancers11091297.
There are few effective therapies for small cell lung cancer (SCLC), a highly aggressive disease representing 15% of total lung cancers. With median survival <2 years, SCLC is one of the most lethal cancers. At present, chemotherapies and radiation therapy are commonly used for SCLC management. Few protein-targeted therapies have shown efficacy in improving overall survival; immune checkpoint inhibitors (ICIs) are promising agents, but many SCLC tumors do not express ICI targets such as PD-L1. This article presents an alternative approach to the treatment of SCLC: the use of drug conjugates, where a targeting moiety concentrates otherwise toxic agents in the vicinity of tumors, maximizing the differential between tumor killing and the cytotoxicity of normal tissues. Several tumor-targeted drug conjugate delivery systems exist and are currently being actively tested in the setting of SCLC. These include antibody-drug conjugates (ADCs), radioimmunoconjugates (RICs), small molecule-drug conjugates (SMDCs), and polymer-drug conjugates (PDCs). We summarize the basis of action for these targeting compounds, discussing principles of construction and providing examples of effective versus ineffective compounds, as established by preclinical and clinical testing. Such agents may offer new therapeutic options for the clinical management of this challenging disease in the future.
小细胞肺癌(SCLC)是一种侵袭性很强的疾病,占肺癌总数的15%,目前针对它的有效治疗方法很少。SCLC的中位生存期小于2年,是最致命的癌症之一。目前,化疗和放疗是SCLC治疗中常用的方法。很少有蛋白质靶向疗法在提高总生存期方面显示出疗效;免疫检查点抑制剂(ICIs)是很有前景的药物,但许多SCLC肿瘤不表达ICIs靶点,如PD-L1。本文提出了一种治疗SCLC的替代方法:使用药物偶联物,其中靶向部分将原本有毒的药物集中在肿瘤附近,使肿瘤杀伤与正常组织细胞毒性之间的差异最大化。目前存在几种肿瘤靶向药物偶联物递送系统,并且正在SCLC的背景下积极进行测试。这些包括抗体-药物偶联物(ADCs)、放射免疫偶联物(RICs)、小分子-药物偶联物(SMDCs)和聚合物-药物偶联物(PDCs)。我们总结了这些靶向化合物的作用基础,讨论了构建原则,并提供了经临床前和临床测试确定的有效与无效化合物的实例。这类药物未来可能为这种具有挑战性的疾病的临床管理提供新的治疗选择。
Cancers (Basel). 2023-11-10
Cancers (Basel). 2023-8-8
Transl Lung Cancer Res. 2015-10
Am J Cancer Res. 2022-3-15
Clin Cancer Res. 2016-10-15
Clin Adv Hematol Oncol. 2021-10
Medicine (Baltimore). 2025-1-17
Nat Commun. 2023-6-1
Cancer Drug Resist. 2021-3-19
J Hematol Oncol. 2019-6-18
Onco Targets Ther. 2019-3-1
J Thorac Oncol. 2019-2-5
CA Cancer J Clin. 2019-1-8
Eur J Med Chem. 2018-12-16
J Natl Compr Canc Netw. 2018-10
N Engl J Med. 2018-9-25