Percorrer por autor "Silvestre, Daniela de Matos Galveias"
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- Upcoming mTOR signalling inhibitors in gastric cancer treatment: a sistemátic review of preclinical studiesPublication . Silvestre, Daniela de Matos Galveias; Marques-Ramos, Ana; Mendes, PriscilaABSTRACT Context: According to the International Agency for Research on Cancer, gastric cancer (GC) is the fifth most prevalent type of cancer in Europe and has the sixth highest mortality rate. In Portugal, it ranks as the fourth most common cancer and the third leading cause of cancer-related death. mTOR is a protein that, under normal conditions, regulates fundamental cellular activities; however, its overexpression is associated with various pathologies, including cancer. As such, the study of mTOR inhibitors has become a promising therapeutic alternative, supported by numerous in vivo and in vitro studies evaluating their efficacy and safety in the treatment of gastric cancer—examples include Everolimus, OSI-027, 2,6-DMBQ, Temsirolimus, and corosolic acid. Given these findings, the main aim of this review is to analyse and synthesise the currently available information from preclinical in vitro and in vivo studies investigating mTOR pathway inhibitors for the treatment of gastric cancer. Methods: Following the application of the search expression, only non-clinical in vitro and in vivo studies published between January 2013 and May 2025 were considered. Results: Fourteen articles were included based on the established criteria. Among the inhibitors analysed, Everolimus was the most extensively studied and showed the most promising results in preclinical models of gastric cancer. It demonstrated consistent efficacy in vitro (10–100 nM, 24–72 hours) and in vivo (5–10 mg/kg/day, 2–4 weeks, orally), with reductions observed in markers such as p-mTOR, p70S6K, and p-AKT. Combination with other drugs (such as cisplatin and chloroquine) enhanced its therapeutic effect. Other inhibitors, including Temsirolimus, OSI-027, 2,6-DMBQ, and Rapamycin, also showed potential but were less frequently studied and supported by more limited data. Conclusion: Among the inhibitors assessed, Everolimus emerged as the most effective, demonstrating consistent antiproliferative effects in both in vitro and in vivo settings, particularly when used in combination with other agents. These findings support the potential of Everolimus as a promising therapeutic option for the treatment of gastric cancer.