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Updated: Nov 22, 2025
Author Spotlight: Establishing a Murine Non-Small Cell Lung Cancer Model for Developing Nanoformulations of Anticancer Drugs
Published on: May 10, 2024
Nelfinavir Inhibits the Growth of Small-cell Lung Cancer Cells and Patient-derived Xenograft Tumors
Shigeru Kawabata1, Nick Connis2, Joell J Gills2
1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. pa1030@osaka-med.ac.jp.
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.
Insights
The HIV drug nelfinavir effectively reduced small-cell lung cancer (SCLC) cell growth and tumor development in preclinical models. This suggests nelfinavir could be a promising new treatment for SCLC patients.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with a poor prognosis and high recurrence rates.
- Current chemotherapy regimens offer limited long-term efficacy for SCLC.
- There is a critical need for novel therapeutic agents and molecular targets for SCLC treatment.
Purpose of the Study:
- To investigate the anti-cancer effects of nelfinavir, an HIV protease inhibitor, against SCLC.
- To evaluate nelfinavir's efficacy in both in vitro SCLC cell cultures and in vivo patient-derived xenograft (PDX) mouse models.
Main Methods:
- Nelfinavir's impact on SCLC cell proliferation and survival was assessed in vitro.
- Preclinical studies involved treating SCLC PDX mouse models with nelfinavir.
- Mechanisms of action, including the unfolded protein response (UPR), mTOR signaling, and ASCL1 expression, were analyzed.
Main Results:
- Nelfinavir demonstrated potent inhibition of SCLC cell proliferation and induced cell death in vitro.
- In vivo studies showed significant inhibition of SCLC PDX tumor growth with nelfinavir treatment.
- These effects were associated with UPR induction, suppressed mTOR activation, and reduced ASCL1 expression.
Conclusions:
- Nelfinavir exhibits significant anti-cancer activity against SCLC in both in vitro and in vivo preclinical settings.
- The findings support the potential of nelfinavir as a therapeutic option for SCLC.
- Further investigation through clinical trials is warranted to evaluate nelfinavir for SCLC patient treatment.
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