Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors
Abstract cGAS-STING pathway stands at the forefront of innate immunity and plays a critical role in regulating adaptive immune responses, making it as a key orchestrator of anti-tumor immunity. Despite the great potential, clinical outcomes with cGAS-STING activators have been disappointing due to t...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-12-01
|
| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-024-02186-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846101397102133248 |
|---|---|
| author | Xiaohong Ying Qiaohui Chen Yongqi Yang Ziyu Wu Wan Zeng Chenxi Miao Qiong Huang Kelong Ai |
| author_facet | Xiaohong Ying Qiaohui Chen Yongqi Yang Ziyu Wu Wan Zeng Chenxi Miao Qiong Huang Kelong Ai |
| author_sort | Xiaohong Ying |
| collection | DOAJ |
| description | Abstract cGAS-STING pathway stands at the forefront of innate immunity and plays a critical role in regulating adaptive immune responses, making it as a key orchestrator of anti-tumor immunity. Despite the great potential, clinical outcomes with cGAS-STING activators have been disappointing due to their unfavorable in vivo fate, signaling an urgent need for innovative solutions to bridge the gap in clinical translation. Recent advancements in nanotechnology have propelled cGAS-STING-targeting nanomedicines to the cutting-edge of cancer therapy, leveraging precise drug delivery systems and multifunctional platforms to achieve remarkable region-specific biodistribution and potent therapeutic efficacy. In this review, we provide an in-depth exploration of the molecular mechanisms that govern cGAS-STING signaling and its potential to dynamically modulate the anti-tumor immune cycle. We subsequently introduced several investigational cGAS-STING-dependent anti-tumor agents and summarized their clinical trial progress. Additionally, we provided a comprehensive review of the unique advantages of cGAS-STING-targeted nanomedicines, highlighting the transformative potential of nanotechnology in this field. Furthermore, we comprehensively reviewed and comparatively analyzed the latest breakthroughs cGAS-STING-targeting nanomedicine, focusing on strategies that induce cytosolic DNA generation via exogenous DNA delivery, chemotherapy, radiotherapy, or dynamic therapies, as well as the nanodelivery of STING agonists. Lastly, we discuss the future prospects and challenges in cGAS-STING-targeting nanomedicine development, offering new insights to bridge the gap between mechanistic research and drug development, thereby opening new pathways in cancer treatment. |
| format | Article |
| id | doaj-art-41f6ecffcd2142a2865e197e4cd03405 |
| institution | Kabale University |
| issn | 1476-4598 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-41f6ecffcd2142a2865e197e4cd034052024-12-29T12:12:17ZengBMCMolecular Cancer1476-45982024-12-0123114310.1186/s12943-024-02186-6Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumorsXiaohong Ying0Qiaohui Chen1Yongqi Yang2Ziyu Wu3Wan Zeng4Chenxi Miao5Qiong Huang6Kelong Ai7Department of Pharmacy, Xiangya Hospital, Central South UniversityDepartment of Pharmacy, Xiangya Hospital, Central South UniversityXiangya School of Pharmaceutical Sciences, Central South UniversityXiangya School of Pharmaceutical Sciences, Central South UniversityXiangya School of Pharmaceutical Sciences, Central South UniversityXiangya School of Pharmaceutical Sciences, Central South UniversityDepartment of Pharmacy, Xiangya Hospital, Central South UniversityXiangya School of Pharmaceutical Sciences, Central South UniversityAbstract cGAS-STING pathway stands at the forefront of innate immunity and plays a critical role in regulating adaptive immune responses, making it as a key orchestrator of anti-tumor immunity. Despite the great potential, clinical outcomes with cGAS-STING activators have been disappointing due to their unfavorable in vivo fate, signaling an urgent need for innovative solutions to bridge the gap in clinical translation. Recent advancements in nanotechnology have propelled cGAS-STING-targeting nanomedicines to the cutting-edge of cancer therapy, leveraging precise drug delivery systems and multifunctional platforms to achieve remarkable region-specific biodistribution and potent therapeutic efficacy. In this review, we provide an in-depth exploration of the molecular mechanisms that govern cGAS-STING signaling and its potential to dynamically modulate the anti-tumor immune cycle. We subsequently introduced several investigational cGAS-STING-dependent anti-tumor agents and summarized their clinical trial progress. Additionally, we provided a comprehensive review of the unique advantages of cGAS-STING-targeted nanomedicines, highlighting the transformative potential of nanotechnology in this field. Furthermore, we comprehensively reviewed and comparatively analyzed the latest breakthroughs cGAS-STING-targeting nanomedicine, focusing on strategies that induce cytosolic DNA generation via exogenous DNA delivery, chemotherapy, radiotherapy, or dynamic therapies, as well as the nanodelivery of STING agonists. Lastly, we discuss the future prospects and challenges in cGAS-STING-targeting nanomedicine development, offering new insights to bridge the gap between mechanistic research and drug development, thereby opening new pathways in cancer treatment.https://doi.org/10.1186/s12943-024-02186-6cGAS-STING pathwayCancer immunotherapyNanomedicinesExDNAChemotherapyRT |
| spellingShingle | Xiaohong Ying Qiaohui Chen Yongqi Yang Ziyu Wu Wan Zeng Chenxi Miao Qiong Huang Kelong Ai Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors Molecular Cancer cGAS-STING pathway Cancer immunotherapy Nanomedicines ExDNA Chemotherapy RT |
| title | Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors |
| title_full | Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors |
| title_fullStr | Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors |
| title_full_unstemmed | Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors |
| title_short | Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform ‘cold’ tumors into ‘hot’ tumors |
| title_sort | nanomedicines harnessing cgas sting pathway sparking immune revitalization to transform cold tumors into hot tumors |
| topic | cGAS-STING pathway Cancer immunotherapy Nanomedicines ExDNA Chemotherapy RT |
| url | https://doi.org/10.1186/s12943-024-02186-6 |
| work_keys_str_mv | AT xiaohongying nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT qiaohuichen nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT yongqiyang nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT ziyuwu nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT wanzeng nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT chenximiao nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT qionghuang nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors AT kelongai nanomedicinesharnessingcgasstingpathwaysparkingimmunerevitalizationtotransformcoldtumorsintohottumors |