Fibroblast growth factor receptors (FGFRs) play key roles in promoting the proliferation, differentiation, and migration of cancer cell. Inactivation of FGFRs by tyrosine kinase inhibitors (TKI) has achieved great success in tumor-targeted therapy. However, resistance to FGFR-TKI has become a concern. Here, we review the mechanisms of FGFR-TKI resistance in cancer, including gatekeeper mutations, alternative signaling pathway activation, lysosome-mediated TKI sequestration, and gene fusion. In addition, we summarize strategies to overcome resistance, including developing covalent inhibitors, developing dual-target inhibitors, adopting combination therapy, and targeting lysosomes, which will facilitate the transition to precision medicine and individualized treatment.

Angiogenesis, a crucial process in tumor growth and metastasis, necessitates targeted therapeutic intervention. This review reviews the latest knowledge of anti-angiogenesis targets in tumors, with emphasis on the molecular mechanisms and signaling pathways that regulate this process. We emphasize the tumor microenvironment's role in angiogenesis, examine endothelial cell metabolic changes, and evaluated potential therapeutic strategies targeting the tumor vascular system. At the same time, we analyzed the signaling pathway and molecular mechanism of tumor angiogenesis in detail. In addition, this paper also looks at the development trend of tumor anti-angiogenesis drugs, including their future development direction and challenges, aiming to provide prospective insight into the development of this field. Despite their potential, anti-angiogenic therapies encounter challenges like drug resistance and side effects, necessitating ongoing research to enhance cancer treatment strategies and the efficacy of these therapies.

T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide–MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

Microliposome maintenance (MCM) 2, MCM3, MCM4, MCM5, MCM6, and MCM7 are DNA replication regulators and are involved in the progression of multiple cancer types, but their role in ovarian cancer is still unclear. The purpose of this study is to clarify the biological function and prognostic value of the MCM complex in ovarian cancer (OS) progression. We analyzed DNA alterations, mRNA and protein levels, protein structure, PPI network, functional enrichment, and prognostic value in OC based on the Oncomine, cBioPortal, TCGA, CPTAC, PDB, GeneMANIA, DAVID, KEGG, and GSCALite databases. The results indicated that the protein levels of these DNA replication regulators were increased significantly. Moreover, survival analysis showed a prognostic signature based on the MCM complex, which performed moderately well in terms of OS prognostic prediction. Additionally, protein structure, functional enrichment, and PPI network analyses indicated that the MCM complex synergistically promoted OC progression by accelerating DNA replication and the cell cycle. In conclusion, our study suggested that the MCM complex might be a potential target and prognostic marker for OC patients.

Vigorous CD8⁺ T cells play a crucial role in recognizing tumor cells and combating solid tumors. How T cells efficiently recognize and target tumor antigens, and how they maintain the activity in the “rejection” of solid tumor microenvironment, are major concerns. Recent advances in understanding of the immunological trajectory and lifespan of CD8⁺ T cells have provided guidance for the design of more optimal anti-tumor immunotherapy regimens. Here, we review the newly discovered methods to enhance the function of CD8⁺ T cells against solid tumors, focusing on optimizing T cell receptor (TCR) expression, improving antigen recognition by engineered T cells, enhancing signal transduction of the TCR-CD3 complex, inducing the homing of polyclonal functional T cells to tumors, reversing T cell exhaustion under chronic antigen stimulation, and reprogramming the energy and metabolic pathways of T cells. We also discuss how to participate in the epigenetic changes of CD8⁺ T cells to regulate two key indicators of anti-tumor responses, namely effectiveness and persistence.