Tumor-targeted drug conjugates as an emerging novel therapeutic approach in small cell lung cancer (Sclc)

Alexander Y. Deneka*, Erica A. Golemis, Yanis Boumber, Tim Beck

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1297
JournalCancers
Volume11
Issue number9
DOIs
StatePublished - Sep 2019
Externally publishedYes

Keywords

  • Antibody-drug conjugates
  • Small cell lung cancer
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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