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Deneka AY , Boumber Y , Beck T , Golemis EA
Tumor-Targeted Drug Conjugates as an Emerging Novel Therapeutic Approach in Small Cell Lung Cancer (SCLC)
Cancers (Basel). 2019 Sep 3;11(9)
PMID: 31484422    PMCID: PMC6769513    URL: https://www.ncbi.nlm.nih.gov/pubmed/31484422
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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.
Deneka, Alexander Y Boumber, Yanis Beck, Tim Golemis, Erica A R21 CA181287/NH/NIH HHS/United States R01 DK108195/NH/NIH HHS/United States 18-75-00104/Russian Science Foundation R01 CA218802/NH/NIH HHS/United States R21 CA223394/NH/NIH HHS/United States Core Grant P30 CA006927/CA/NCI NIH HHS/United States Journal Article Review Switzerland Cancers (Basel). 2019 Sep 3;11(9). pii: cancers11091297. doi: 10.3390/cancers11091297.