Objective: This review describes the comprehensive portrait of tumor microenvironment (TME). Additionally, we provided a panoramic perspective on the transformation and functions of the diverse constituents in TME, and the underlying mechanisms of drug resistance, beginning with the immune cells and metabolic dynamics within TME. Lastly, we summarized the most auspicious potential therapeutic strategies.
Results: TME is a unique realm crafted by malignant cells to withstand the onslaught of endogenous and exogenous therapies. Recent research has revealed many small-molecule immunotherapies exhibiting auspicious outcomes in preclinical investigations. Furthermore, some pro-immune mechanisms have emerged as a potential avenue. With the advent of nanosystems and precision targeting, targeted therapy has now transcended the "comfort zone" erected by cancer cells within TME.
Conclusion: The ceaseless metamorphosis of TME fosters the intransigent resilience and proliferation of tumors. However, existing therapies have yet to surmount the formidable obstacles posed by TME. Therefore, scientists should investigate potential avenues for therapeutic intervention and design innovative pharmacological and clinical technologies.
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http://dx.doi.org/10.2174/1568009623666230712095021 | DOI Listing |
J Transl Med
January 2025
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Background: Drug resistance constitutes one of the principal causes of poor prognosis in breast cancer patients. Although cancer cells can maintain viability independently of mitochondrial energy metabolism, they remain reliant on mitochondrial functions for the synthesis of new DNA strands. This dependency underscores a potential link between mitochondrial energy metabolism and drug resistance.
View Article and Find Full Text PDFNPJ Breast Cancer
January 2025
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Early-stage and metastatic breast cancers (MBC) can exhibit genomic heterogeneity, even within the same individual. Response to therapy in metastatic breast cancer patients with multiple metastases can also be heterogeneous, with different degrees of responsiveness to the same drug(s) across metastatic sites, termed "mixed response," within the same patient. Whether this treatment response variability is influenced by factors such as intrinsic tumor characteristics of metastatic lesions and/or the microenvironment is unknown.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Oncolytic viruses (OVs) emerge as a promising cancer immunotherapy. However, the temporal impact on tumor cells and the tumor microenvironment, and the nature of anti-tumor immunity post-therapy remain largely unclear. Here we report that CD4 T cells are required for durable tumor control in syngeneic murine models of glioblastoma multiforme after treatment with an oncolytic herpes simplex virus (oHSV) engineered to express IL-12.
View Article and Find Full Text PDFActa Biomater
January 2025
School of Materials and Energy, Southwest University, Chongqing 400715, China; Yibin Academy of Southwest University, Yibin 644005, China. Electronic address:
Glioblastoma (GBM) is a primary central nervous system neoplasm, characterized by a grim prognosis and low survival rates. This unfavorable therapeutic outcome is partially attributed to the inadequate immune infiltration and an immunosuppressive microenvironment, which compromises the effectiveness of conventional radiotherapy and chemotherapy. To this end, precise modulation of cellular dynamics in the immune system has emerged as a promising approach for therapeutic intervention.
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