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Natural compounds for non-small cell lung cancer treatment: focus on the EGFR signaling pathway
Abstract:
The EGFR signaling pathway is a critical driver in the occurrence and development of non-small cell lung cancer (NSCLC). However, the inevitable development of acquired resistance to EGFR tyrosine kinase inhibitor (TKI) poses a major therapeutic challenge. Natural compounds, with their intrinsic multi-target capabilities and favorable safety profiles, represent a promising strategy for overcoming this resistance. This review provides a critical synthesis of current evidence for over 33 representative natural compounds-spanning alkaloids, terpenoids, flavonoids, and polyphenols-with a focus on their mechanisms for enhancing TKI efficacy. These include direct inhibition of EGFR activation, regulation of key downstream signaling pathways, and induction of programmed cell death. Furthermore, it also examine how emerging approaches such as nano-delivery systems can overcome the pharmacokinetic limitations of these compounds. Ultimately, this review provides a novel, strategy-oriented perspective by framing natural compounds not merely as standalone agents, but as essential components of rational combination therapies, thereby offering a fresh roadmap for their clinical translation in precision oncology for NSCLC.
Insights
Natural compounds show promise in overcoming resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). This review explores their mechanisms and potential in combination therapies for precision oncology.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Epidermal Growth Factor Receptor (EGFR) signaling is crucial in non-small cell lung cancer (NSCLC).
- Acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) presents a significant clinical challenge.
- Natural compounds offer multi-target capabilities and favorable safety profiles for overcoming TKI resistance.
Purpose of the Study:
- To review natural compounds that enhance EGFR TKI efficacy in NSCLC.
- To elucidate the mechanisms by which natural compounds overcome TKI resistance.
- To explore the potential of natural compounds in combination therapies and nano-delivery systems.
Main Methods:
- Literature review synthesizing evidence on over 33 natural compounds.
- Analysis of mechanisms including direct EGFR inhibition, downstream pathway regulation, and apoptosis induction.
- Examination of nano-delivery systems for improved pharmacokinetics.
Main Results:
- Natural compounds demonstrate diverse mechanisms to enhance TKI efficacy.
- Specific compound classes (alkaloids, terpenoids, flavonoids, polyphenols) are effective.
- Nano-delivery systems can mitigate pharmacokinetic limitations.
Conclusions:
- Natural compounds are valuable in combination therapies to overcome EGFR TKI resistance in NSCLC.
- This strategy offers a roadmap for clinical translation in precision oncology.
- Further research into combination approaches with natural compounds is warranted.
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