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Updated: Apr 11, 2026
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Sulforaphane attenuates EGFR signaling in NSCLC cells
Chi-Yuan Chen1,2, Zhu-Yun Yu1, Yen-Shu Chuang1
1Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Tao-Yuan, 333, Taiwan.
Background:
EGFR, a receptor tyrosine kinase (RTK), is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of many cancers, including NSCLC. However, intrinsic and acquired resistance to TKI remains a common obstacle. One strategy that may help overcome EGFR-TKI resistance is to target EGFR for degradation. As EGFR is a client protein of heat-shock protein 90 (HSP90) and sulforaphane is known to functionally regulate HSP90, we hypothesized that sulforaphane could attenuate EGFR-related signaling and potentially be used to treat NSCLC.
Results:
Our study revealed that sulforaphane displayed antitumor activity against NSCLC cells both in vitro and in vivo. The sensitivity of NSCLC cells to sulforaphane appeared to positively correlate with the inhibition of EGFR-related signaling, which was attributed to the increased proteasomal degradation of EGFR. Combined treatment of NSCLC cells with sulforaphane plus another HSP90 inhibitor (17-AAG) enhanced the inhibition of EGFR-related signaling both in vitro and in vivo.
Conclusions:
We have shown that sulforaphane is a novel inhibitory modulator of EGFR expression and is effective in inhibiting the tumor growth of EGFR-TKI-resistant NSCLC cells. Our findings suggest that sulforaphane should be further explored for its potential clinical applications against NSCLC.
Insights
Sulforaphane shows promise in treating non-small cell lung cancer (NSCLC) by degrading epidermal growth factor receptor (EGFR). This natural compound effectively inhibits tumor growth in EGFR-TKI-resistant NSCLC, suggesting potential clinical applications.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) is often overexpressed/mutated in non-small cell lung cancer (NSCLC).
- Resistance to EGFR tyrosine kinase inhibitors (TKIs) is a significant clinical challenge.
- Targeting EGFR for degradation is a potential strategy to overcome TKI resistance.
Purpose of the Study:
- To investigate the potential of sulforaphane, a known regulator of heat-shock protein 90 (HSP90), in treating NSCLC.
- To determine if sulforaphane can attenuate EGFR-related signaling and overcome EGFR-TKI resistance.
Main Methods:
- Evaluated sulforaphane's antitumor activity in NSCLC cells in vitro and in vivo.
- Assessed the correlation between sulforaphane sensitivity and EGFR signaling inhibition.
- Investigated the role of proteasomal degradation in sulforaphane's mechanism.
- Examined the effects of combined sulforaphane and 17-AAG (an HSP90 inhibitor) treatment.
Main Results:
- Sulforaphane demonstrated significant antitumor activity against NSCLC cells.
- Sulforaphane treatment led to increased proteasomal degradation of EGFR, inhibiting EGFR-related signaling.
- Combined treatment with sulforaphane and 17-AAG enhanced EGFR signaling inhibition.
Conclusions:
- Sulforaphane acts as a novel inhibitor of EGFR expression and effectively suppresses tumor growth in EGFR-TKI-resistant NSCLC.
- These findings highlight sulforaphane as a potential therapeutic agent for NSCLC, warranting further clinical investigation.
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