Pindiprolu Sai Kiran S S, Singh Madhu Tanya, Magham Sai Varshini, Kumar Chirravuri S Phani, Dasari Nagasen, Gummadi Ramakrishna, Krishnamurthy Praveen Thaggikuppe
School of Pharmacy, Aditya University, Surampalem, Andhra Pradesh, India.
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, 20, Rocklands, Ooty, 643001, The Nilgiris, Tamil Nadu, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb 5. doi: 10.1007/s00210-025-03835-3.
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.
环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白（cGAS-STING）信号通路在三阴性乳腺癌（TNBC）的肿瘤微环境（TME）免疫反应中发挥重要作用。cGAS-STING信号通路的急性且可控激活导致肿瘤抑制，而cGAS-STING信号通路的慢性激活则导致免疫抑制性TME，这可能导致肿瘤存活。因此，需要开发治疗策略，以利用cGAS-STING信号通路的肿瘤抑制作用，同时将与慢性激活相关的风险降至最低。联合疗法和基于纳米载体递送cGAS-STING激动剂已成为癌症免疫治疗中可控调节cGAS-STING信号通路的有前景的策略。这些方法旨在优化cGAS-STING通路的肿瘤抑制作用，同时将与cGAS-STING信号通路调节剂相关的挑战降至最低。在本综述中，我们讨论了联合疗法和基于纳米载体的递送系统在癌症免疫治疗中有效控制cGAS-STING信号通路的最新进展和策略。此外，我们强调了基于纳米载体的方法对于有效靶向cGAS-STING信号通路、应对耐药机制以及克服免疫抑制、肿瘤异质性和脱靶效应等关键挑战的重要性。
