Discussion
tumor, pneumonia, cancers, stomatitis, hyperlipidemia, toxicities, cancer, hepatotoxicity, sarcoma, Cancer
TUMOR, PNEUMONIA, CANCERS, STILL, HYPERLIPIDEMIA, STOMATITIS, CANCER, DISEASE, HYPERGLYCEMIA, SARCOMA, BONE MARROW SUPPRESSION, NEUROENDOCRINE CARCINOMA, CANCER
The discovery of mTOR represents a fundamental breakthrough in the understanding of cell growth, metabolism, and disease [The serious toxicities of PI3K/AKT/mTOR inhibitors limit their clinical use and approval, including hyperglycemia, hyperlipidemia, bone marrow suppression, pneumonia, stomatitis, and hepatotoxicity [The PK profile showed that LXI-15029 was absorbed rapidly, and the arithmetic mean of tMany studies aim to understand the potential resistance mechanisms of mTOR-targeted therapies, which is necessary for the rational application of mTOR inhibitors for the effective treatment of cancer. mTOR inhibitors interrupt the phosphorylation of substrates and block relevant signal transduction, thereby inhibiting the cell cycle, tumor metabolism, and cell survival and exerting antitumor effects through binding with the mTOR binding site [Cancer immunotherapy is another promising approach for mTOR dual blockers. Cell-based and in vivo research showed that mTOR inhibitors can enhance the efficacy of various tumor immunotherapy methods by elevating PD-L1 expression in tumor cells and inhibiting the activation of T memory cells [Notably, about 50% of the participants had rare cancers such as sarcoma and neuroendocrine carcinoma, which have achieved few treatment breakthroughs. The results in this study suggest favorable efficacy for these rare cancers. Still, patients who are more likely to benefit from mTOR inhibitors remain to be further explored. Patients resistant to targeted therapy such as epidermal growth factor receptor tyrosine kinases inhibitors might be potential beneficiaries since they often have activation of the PI3K/AKT/mTOR pathway. Moreover, some ongoing clinical trials could suggest that mTOR dual inhibition might be beneficial in patients harboring NFE 2L2, STK11, RICTOR, or other specific genetic alterations (NCT04518137) or combined with anti-PD-1 antibody (NCT04337463) or antineoplastic exportin-1 (XPO1) inhibitors (NCT04998760) [The limitations of this study included the small sample size, the single-center design, and the lack of tissue and serum collection before and during the study. Collection of tissue and serum samples in future studies would allow exploring predictive biomarkers and facilitate observing the changes in the PI3K/AKT/mTOR signaling pathway and related specific genetic alterations, which will further improve treatment strategies and guide the better selection of responsive patients [