# Enhancing Chemosensitivity With Quercetin: Mechanistic Insights Into MerTK and Associated Signaling Pathways

**Authors:** Sorush Jafari, Sorayya Ghasemi

PMC · DOI: 10.1002/cnr2.70370 · Cancer Reports · 2025-11-06

## TL;DR

Quercetin, a natural compound, may improve cancer treatment by targeting the MerTK pathway and could be more effective with better delivery methods.

## Contribution

This paper reviews quercetin's role in modulating MerTK and its potential as a supplement in cancer therapy when combined with advanced delivery systems.

## Key findings

- Quercetin modulates MerTK-mediated pathways to reduce tumor progression and immune evasion.
- Nanoparticle delivery systems can enhance quercetin's bioavailability for clinical use.
- Combining quercetin with MerTK inhibitors may improve cancer treatment efficacy.

## Abstract

Quercetin, a natural flavonoid, has established significant anticancer properties through its antioxidant, anti‐inflammatory, and signaling pathway modulation effects. However, due to the issues with absorption and insufficient bioavailability, its clinical usefulness is still restricted. The purpose of this review is to review quercetin's potential as a new supplemental treatment for cancer, with a focus on the myeloid‐epithelial‐reproductive tyrosine kinase (MerTK) pathway and the downstream signaling cascades. We study ways to improve its clinical usefulness by resolving its limitations.

To examine research on quercetin's mechanisms of action, its impact on MerTK and downstream pathways, and the application of efficient drug delivery technologies, a thorough literature analysis was carried out. Quercetin effectively modulates MerTK‐mediated signaling pathways, reducing tumor progression, angiogenesis, and immune evasion. It suppresses PD‐L1 expression, inhibits cancer stem cell maintenance, and enhances apoptosis. Emerging evidence suggests nanoparticle‐based delivery systems can improve querecetin's bioavailability, enabling its integration into combination therapies alongside MerTK inhibitors.

Quercetin holds great promise as a complementary therapeutic agent targeting MerTK and associated signaling pathways. Advanced delivery systems and combination strategies with MerTK inhibitors can overcome its clinical limitations and enhance its efficacy in cancer therapies. Future studies, particularly clinical trials, are needed to validate these findings and optimize quercetin's translational potential.

## Linked entities

- **Proteins:** MERTK (MER proto-oncogene, tyrosine kinase), CD274 (CD274 molecule)
- **Chemicals:** quercetin (PubChem CID 5280343)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, MERTK (MER proto-oncogene, tyrosine kinase) [NCBI Gene 10461] {aka MER, RP38, Tyro12, c-Eyk, c-mer}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}
- **Diseases:** inflammatory (MESH:D007249), cancer (MESH:D009369)
- **Chemicals:** Quercetin (MESH:D011794), querecetin (-), flavonoid (MESH:D005419)

## Full text

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## Figures

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## References

124 references — full list in the complete paper: https://tomesphere.com/paper/PMC12590157/full.md

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Source: https://tomesphere.com/paper/PMC12590157