While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.
2 May 2025 in International Journal of Biological Macromolecules
Circular RNAs (circRNAs) are recognized as a novel type of single-stranded endogenous noncoding RNA molecule with the characteristics of tissue specificity, sequence conservation and structural stability. Accumulating studies have shown that circRNAs play a unique biological role in different kinds of diseases. CircRNAs can affect tumor proliferation, migration, metastasis and other behaviors by modulating the expression of downstream genes. CircSMARCA5, an example of a circRNA, is dysregulated in various noninfectious diseases, such as tumors, osteoporosis, atherosclerosis and coronary heart disease. Furthermore, recent studies have demonstrated that circSMARCA5 is associated with the occurrence and development of a variety of tumors, including gastric cancer, glioblastoma, hepatocellular carcinoma, multiple myeloma, colorectal cancer, breast cancer and osteosarcoma. Mechanistically, circSMARCA5 primarily acts as a sponge of miRNAs to regulate the expression of downstream genes, and can serve as a potential biomarker for the diagnosis of malignant tumors. This review summarizes the biological roles of circSMARCA5 and its molecular mechanism of action in various diseases. Moreover, the meta-analysis of some publications showed that the expression of circSMARCA5 was significantly correlated with the prognosis of patients and tumor TNM stage, showing that circSMARCA5 has the potential to be a prognostic marker.
Bladder cancer (BCa) is a malignant tumor that occurs in the bladder mucosa with high mortality. Circular RNAs (circRNAs), as newly discovered noncoding RNAs, are associated with the occurrence and development of BCa. However, the effects of circRNAs in BCa have not been fully elucidated. Through the GEO (Gene Expression Omnibus) database, an abnormally expressed circular RNA, circHGS (hsa_circ_0004721), was first identified in BCa. qRT – PCR was performed to measure the expression of circHGS in BCa tissues and cells. The intracellular localization of circHGS was detected by nucleocytoplasmic separation experiment and fluorescence in situ hybridization assay. In vitro experiments were conducted to detect the effects of circHGS on cell cycle, proliferation, migration and invasion. The correlations between miR-513a-5p and circHGS or VEGFC were confirmed by dual-luciferase reporter assay, qRT – PCR and western blot. The role of circHGS in vivo was verified by xenograft tumor mice model. In this study, we clarified the roles and potential mechanism of circHGS in BCa. CircHGS, originating from the HGS gene, is upregulated in BCa tissues compared to normal tissues. Moreover, the expression of circHGS in BCa was positively associated with tumor grade and pathological T stage. Functionally, silencing of circHGS apparently suppressed cell cycle, proliferation, migration and invasion, but circHGS overexpression showed the opposite result. In vivo experiments also suggested that knockdown of circHGS suppressed tumor growth. Mechanistically, circHGS functions as a sponge of miR-513a-5p to elevate VEGFC expression and activate the AKT/mTOR signaling pathway, ultimately promoting BCa progression. Our findings indicated that circHGS promotes BCa progression via the miR-513a-5p/VEGFC/AKT/mTOR pathway and can be a promising therapeutic target of BCa.
25 May 2023 in Frontiers in Cell and Developmental Biology
Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5′caps or 3′polyadenylated tails. Increasing evidence shows that circRNAs may play an important role in tumorigenesis and cancer metastasis. Circ-SHPRH originates from exons 26–29 of the SHPRH gene, and it is closely associated with human cancers. We searched PubMed, Web of Science, and Embase databases for relevant literatures until 24 December 2022. Eighteen research papers were included in this review, and 11 papers were selected for meta-analysis after screening. Three eligible published studies about circ-SHPRH were enrolled based on their tumor diagnosis aspect, 7 eligible published studies were related to overall survival (OS), and 3 eligible published studies were related to tumor grade. Many studies have shown that circ-SHPRH acts as a miRNA sponge or encodes a protein to regulate downstream genes or signal pathways, and exerts specific biological functions that affect the proliferation, invasion, and apoptosis of cancer cells. Meta-analysis showed that patients with high expression of circ-SHPRH had better OS (HR = 0.53, 95% CI 0.38–0.74, p-value <0.05) and lower TNM stage (HR = 0.33, 95% CI 0.18–0.62, p-value = 0.001). In addition, circ-SHPRH has potential diagnostic value (AUC = 0.8357). This review will help enrich our understanding of the role and mechanism of circ-SHPRH in human cancers. Circ-SHPRH has the potential to be a novel diagnostic and prognostic biomarker for various solid cancers.