Latest update on chemokine receptors as therapeutic targets
1School of Pharmacy, University of East Anglia, Norwich, U.K.
Abstract:
The chemokine system plays a fundamental role in a diverse range of physiological processes, such as homeostasis and immune responses. Dysregulation in the chemokine system has been linked to inflammatory diseases and cancer, which renders chemokine receptors to be considered as therapeutic targets. In the past two decades, around 45 drugs targeting chemokine receptors have been developed, yet only three are clinically approved. The challenging factors include the limited understanding of aberrant chemokine signalling in malignant diseases, high redundancy of the chemokine system, differences between cell types and non-specific binding of the chemokine receptor antagonists due to the broad ligand-binding pockets. In recent years, emerging studies attempt to characterise the chemokine ligand-receptor interactions and the downstream signalling protein-protein interactions, aiming to fine tuning to the promiscuous interplay of the chemokine system for the development of precision medicine. This review will outline the updates on the mechanistic insights in the chemokine system and propose some potential strategies in the future development of targeted therapy.
Insights
The chemokine system is crucial for immune responses but its dysregulation drives diseases like cancer. Understanding chemokine signaling is key to developing effective targeted therapies.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- The chemokine system regulates homeostasis and immune responses.
- Dysregulation of chemokines is implicated in inflammatory diseases and cancer.
- Chemokine receptors are attractive therapeutic targets, but drug development faces challenges.
Purpose of the Study:
- To review recent mechanistic insights into the chemokine system.
- To explore challenges in developing chemokine receptor-targeted therapies.
- To propose future strategies for precision medicine in chemokine-related diseases.
Main Methods:
- Literature review of chemokine system research.
- Analysis of drug development successes and failures.
- Exploration of emerging studies on chemokine signaling pathways.
Main Results:
- Limited understanding of chemokine signaling in cancer hinders drug development.
- High redundancy and cell-type specificity complicate targeted approaches.
- Non-specific binding is a significant issue for chemokine receptor antagonists.
Conclusions:
- Further characterization of chemokine ligand-receptor and protein-protein interactions is needed.
- Fine-tuning the chemokine system's promiscuous interplay is essential for precision medicine.
- New strategies are required to overcome current limitations in developing targeted chemokine therapies.
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