RESUMEN
BACKGROUND AND OBJECTIVE: Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC). METHODS: TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0. KEY FINDINGS AND LIMITATIONS: The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs. CONCLUSIONS: Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC. PATIENT SUMMARY: We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer.
RESUMEN
As the most common internal post-transcriptional RNA modification in eukaryotic cells, N6-methyladenosine (m6 A) performs a dynamic and reversible role in a variety of biological processes mediated by methyltransferases (writers), demethylases (erasers), and m6 A binding proteins (readers). M6 A methylation enables transcriptome conversion in different signals that regulate various physiological activities and organ development. Over the past few years, emerging studies have identified that mRNA m6 A regulators defect in ß-cell leads to abnormal regulation of the target mRNAs, thereby resulting in ß-cell dysfunction and loss of ß-cell identity and mass, which are strongly associated with type 2 diabetes mellitus (T2DM) pathogenesis. Also, mRNA m6 A modification has been implicated with insulin resistance in muscles, fat, and liver cells/tissues. In this review, we elaborate on the biological features of m6 A methylation; provide a comprehensive overview of the underlying mechanisms that how it controls ß-cell function, identity, and mass as well as insulin resistance; highlight its connections to glucose metabolism and lipid metabolism linking to T2DM; and further discuss its role in diabetes complications and its therapeutic potentials for T2DM diagnosis and treatment.