Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment.

The cGAS-STING signaling plays an important role in the immune response in a tumor microenvironment (TME) of triple-negative breast cancer (TNBC). The acute and controlled activation of cGAS-STING signaling results in tumor suppression, while chronic activation of cGAS-STING signaling results in immune-suppressive TME that could result in tumor survival. There is a need, therefore, to develop therapeutic strategies for harnessing tumor suppressive effects of cGAS-STING signaling while minimizing the risks associated with chronic activation. Combination therapies and nanocarriers-based delivery of cGAS-STING agonists have emerged as promising strategies in immunotherapy for controlled modulation of cGAS-STING signaling in cancer. These approaches aim to optimize the tumor suppressive effects of the cGAS-STING pathway while minimizing the challenges associated with modulators of cGAS-STING signaling. In the present review, we discuss recent advancements and strategies in combination therapies and nanocarrier-based delivery systems for effectively controlling cGAS-STING signaling in cancer immunotherapy. Further, we emphasized the significance of nanocarrier-based approaches for effective targeting of the cGAS-STING signaling, tackling resistance mechanisms, and overcoming key challenges like immune suppression, tumor heterogeneity, and off-target effects.