Tumor microenvironment and cellular senescence: Understanding therapeutic resistance and harnessing strategies. (November 2022)

• Record Type: Journal Article
• Authors: Liu, Hanxin; Zhao, Huifang; Sun, Yu
• Is Part Of: Seminars in cancer biology. Volume 86(2023)Part 3
• Page Start: 769
• Page End: 781
• Publication Date: 2022-11
• Subjects: ABC ATP-binding cassette -- ABCB4 ATP-binding cassette subfamily B member 4 -- ALL acute lymphoblastic leukemia -- Alox5 arachidonate 5-lipoxytenase -- APAF1 apoptotic protease-activating factor 1 -- APC antigen-presenting cell -- AREG amphiregulin -- CAA cancer-associated adipocyte -- CAF cancer-associated fibroblast -- CAR chimeric antigen receptor -- CCL2 C-C motif chemokine ligand 2 -- CCR2 C-C motif chemokine receptor 2 -- CDK cyclin-dependent kinase -- cGAS-STING cyclic GMP-AMP synthase-stimulator of interferon gene -- CHI3L1 chitinase-3 like-protein-1 -- CSC cancer stem cell -- CTL cytotoxic T lymphocyte -- CXCL1 C-X-C motif chemokine ligand 1 -- CXCL12 C-X-C motif chemokine ligand 12 -- CXCR1 C-X-C motif chemokine receptor type 1 -- DC dendritic cell -- DDR DNA damage response -- DNA-SCARS DNA segments with chromatin alterations reinforcing senescence -- D+Q dasatinib and quercetin -- ECM extracellular matrix -- EGFL7 epidermal growth factor-like protein 7 -- EMT epithelial-to-mesenchymal transition -- ERα estrogen receptor alpha -- ET-1 endothelin-1 -- EV extracellular vesicle -- FAK focal adhesion kinase -- FAP fibroblast activation protein -- FFA free fatty acid -- FGF2 fibroblast growth factor 2 -- FGFR1 FGF receptor 1 -- GBC gallbladder cancer -- GBM glioblastoma multiforme -- GM-CSF granulocyte-macrophage colony-stimulating factor -- HCC hepatocellular carcinoma -- HGF hepatocyte growth factor -- HIF hypoxia inducible factor -- HNSCC head and neck squamous cell carcinoma -- HSP90 heat shock protein 90 -- HUVEC human umbilical vein cell -- ICB immune checkpoint blockade -- IFN interferon -- IFN-γ interferon gamma -- IL interleukin -- JAK2 activated Janus kinase 2 -- LL lymphoblastic lymphoma -- PD-L1 programmed cell death ligand-1 -- MAPK mitogen-activated protein kinase -- MAPKAPK2 MAPK activated protein kinase 2 -- mCRPC metastatic castration-resistant prostate cancer -- MDR multi-drug resistance -- MDSC myeloid-derived suppressor cell -- miRNA microRNA -- MMP matrix metalloproteinase -- MRD minimal residual disease -- mTOR mammalian target of rapamycin -- NAC neo-adjuvant chemotherapy -- NK natural killer -- NKG2A natural killer group 2A -- NKG2D natural killer group 2D -- NSCLC non-small cell lung cancer -- OIS oncogene-induced senescence -- OXPHOS oxidative phosphorylation -- PAP prostatic acid phosphatase -- PD-1 programmed cell death 1 -- PD-L1 programmed death ligand 1 -- PICS Pten-loss-induced cellular senescence -- PI3K phosphatidylinositol-3-kinase -- PROTAC proteolysis targeting chimera -- RIPK1 receptor interacting protein kinase 1 -- ROS reactive oxygen species -- RS replicative senescence -- SCAP senescent cell anti-apoptotic pathway -- SA-β-gal senescence-associated β galactosidase -- SAHF senescence-associated heterochromatin foci -- SAS senescence-associated stemness -- SASP senescence-associated secretory phenotype -- SCLC small cell lung cancer -- SCM senescent cell-conditioned medium -- scRNA single-cell RNA -- SDF-1 stromal cell-derived factor 1 -- STAT3 signal transducer and activator of transcription 3 -- TAM tumor-associated macrophage -- TAN tumor-associated neutrophil -- TEC tumor endothelial cell -- TGF-β transforming growth factor beta -- Th1 T helper type 1 -- Th2 T helper type 2 -- Tim-3 T cell immunoglobulin domain and mucin domain-3 -- TIS therapy-induced senescence -- TME tumor microenvironment -- TNF-α tumor necrosis factor-alpha -- uNK uterine natural killer -- uPAR urokinase-type plasminogen activator receptor -- VEGF vascular endothelial growth factor -- VEGFR vascular endothelial growth factor receptor; Tumor microenvironment -- Stromal cell -- Cancer resistance -- Senescent cell -- Senotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2021.11.004
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: The tumor microenvironment (TME) is a major contributor to cancer malignancy including development of therapeutic resistance, a process mediated in part through intercellular crosstalk. Besides diverse soluble factors responsible for pro-survival pathway activation, immune evasion and extracellular matrix (ECM) remodeling further promote cancer resistance. Importantly, therapy-induced senescence (TIS) of cells in the TME is frequently observed in anticancer regimens, an off-target effect that can generate profound impacts on disease progression. By conferring the resistance and fueling the repopulation of remaining cancerous cells, TIS is responsible for tumor relapse and distant metastasis in posttreatment stage. This pathological trajectory can be substantially driven by the pro-inflammatory feature of senescent cells, termed as the senescence-associated secretory phenotype (SASP). Targeting strategies to selectively and efficiently remove senescent cells before they exert non-autonomous but largely deleterious effects, are emerging as an effective solution to prevent drug resistance acquired from a treatment-remodeled TME. In this review, we summarize the TME composition and key activities that affect tissue homeostasis and support treatment resistance. Promising opportunities that allow TME-manipulation and senescent cell-targeting (senotherapy) are discussed, with translational pipelines to overcome therapeutic barriers in clinical oncology projected.