Unveiling GST Family: A Critical Player in the Development and Survival of Metastatic Tumors

Cancer metastasis represents a critical challenge in oncology, accounting for over 90% of cancer-related deaths. This review focuses on the complex process of metastasis, detailing key phases including invasion, intravasation, circulation, extravasation, and colonization, each regulated by complex biological and environmental interactions. A central point of discussion is the varied role of glutathione S-transferase theta 1 (GSTT1) in metastasis. Traditionally known for detoxification, GSTT1 contributes to tumor progression by modulating the extracellular matrix (ECM), notably through the glutathionylation of fibronectin, enhancing metastatic cell survival and colonization. Studies reveal GSTT1 is crucial for macrometastases, promoting resistance to chemotherapy via slow-cycling, epithelial-mesenchymal transition-expressing cells. Its expression in circulating tumor cells underscores its pivotal role in later metastatic stages. In preclinical studies, genetic modulation of GSTT1 has shown that its inhibition reduces metastatic burden, presenting GSTT1 as a target for advanced cancer treatment. Additionally, the review examines how polymorphisms in related GST genes, such as GSTM1, influence cancer outcomes, implicating them in prognosis and therapy response. Integrating these findings could lead to revolutionary therapeutic strategies that disrupt GSTT1-mediated pathways, potentially transforming the combat against metastatic disease.