Nelfinavir Inhibits the Growth of Small-cell Lung Cancer Cells and Patient-derived Xenograft Tumors.

Journal Article (Journal Article)

BACKGROUND/AIM: Small-cell lung cancer (SCLC) is aggressive and confers poor prognosis. Although SCLC shows more response to chemotherapy than other types of lung cancer, it is difficult to cure because of its frequent recurrence. New drugs and molecular targets need to be identified. MATERIALS AND METHODS: We investigated the effect of nelfinavir, an HIV protease inhibitor, on SCLC cells and in preclinical treatment studies using SCLC patient-derived xenograft (PDX) mouse models. RESULTS: Nelfinavir inhibited SCLC cell proliferation and induced cell death in vitro, which was caused by induction of the unfolded protein response (UPR), inhibition of mammalian/mechanistic target of rapamycin (mTOR) activation, and reduction in the expression of SCLC-related molecules such as achaete-scute homolog 1 (ASCL1). In vivo, nelfinavir inhibited the growth of SCLC PDX tumors, which correlated with the induction of UPR and reduced expression of ASCL1. CONCLUSION: Nelfinavir is highly effective in SCLC in vitro and in vivo, suggesting possible incorporation of nelfinavir into clinical trials for patients with SCLC.

Full Text

Duke Authors

Cited Authors

  • Kawabata, S; Connis, N; Gills, JJ; Hann, CL; Dennis, PA

Published Date

  • January 2021

Published In

Volume / Issue

  • 41 / 1

Start / End Page

  • 91 - 99

PubMed ID

  • 33419802

Electronic International Standard Serial Number (EISSN)

  • 1791-7530

Digital Object Identifier (DOI)

  • 10.21873/anticanres.14754

Language

  • eng

Conference Location

  • Greece