# Beyond tumour suppression: cGAS‐STING pathway in urologic malignancies: Context‐dependent duality and therapeutic implications

## TL;DR

The cGAS-STING pathway has both tumor-suppressing and pro-tumor roles in urologic cancers, offering new therapeutic strategies.

## Contribution

This study reveals the context-dependent duality of the cGAS-STING pathway in urologic malignancies and proposes new treatment approaches.

## Key findings

- The cGAS-STING pathway can trigger anticancer effects via CD8+ T cell infiltration.
- STING pathway supports prostate cancer growth through regulatory B cells.
- STING modifications contribute to immune escape in renal cell carcinoma.

## Abstract

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon (IFN) genes (STING) pathway emerges as a dual‐functional role in urologic malignancies, exhibiting context‐dependent tumor‐suppressive and pro‐tumorigenic activities. When this pathway is activated in urologic tumors, IFN transcription and CD8+ T cell infiltration are triggered, which has an anticancer effect. However, this pathway facilitates the development of prostate cancer through the up‐regulation of regulatory B cells. STING palmitoylation triggers immune escape in renal cell carcinoma, and the STING/SLC14A1 axis also mediates chemoresistance in bladder cancer.

Based on these findings, we establish the first systematic comparison of tissue‐specific STING regulation in urological malignancies, challenging the conventional tumor suppressor‐centric view. This review also highlights several innovative strategies leveraging this duality during urologic cancers. The demand for the long‐term safety and effectiveness of these targeted STING treatments has not been fully met.

This study introduces a framework that harnesses the dual functions of the cGAS‐STING pathway to strengthen immunotherapy approaches and improve clinical outcomes to bridge the pre‐clinical‐clinical gap.

The context‐dependent duality of cGAS–STING signalling in urologic tumours is revealed.Targeting the STING pathway, in combination with immunotherapies and gene therapies, enhances the anti‐tumour response.Sex hormone differences in urological malignancies are correlated with the cGAS–STING pathway.

The context‐dependent duality of cGAS–STING signalling in urologic tumours is revealed.

Targeting the STING pathway, in combination with immunotherapies and gene therapies, enhances the anti‐tumour response.

Sex hormone differences in urological malignancies are correlated with the cGAS–STING pathway.

The context‐dependent duality of cGAS–STING signalling in urologic tumours is revealed.Targeting the STING pathway, in combination with immunotherapies and gene therapies, enhances the anti‐tumour response.Sex hormone differences in urological malignancies are correlated with the cGAS–STING pathway.

The context‐dependent duality of cGAS–STING signalling in urologic tumours is revealed.

Targeting the STING pathway, in combination with immunotherapies and gene therapies, enhances the anti‐tumour response.

Sex hormone differences in urological malignancies are correlated with the cGAS–STING pathway.