Disseminated cancer cells in breast cancer: Mechanism of dissemination and dormancy and emerging insights on therapeutic opportunities. (January 2022)

• Record Type: Journal Article
• Authors: Ramamoorthi, Ganesan; Kodumudi, Krithika; Gallen, Corey; Zachariah, Nadia Nocera; Basu, Amrita; Albert, Gabriella; Beyer, Amber; Snyder, Colin; Wiener, Doris; Costa, Ricardo L.B.; Czerniecki, Brian J.
• Is Part Of: Seminars in cancer biology. Volume 78(2022)
• Page Start: 78
• Page End: 89
• Publication Date: 2022-01
• Subjects: DCCs Disseminated cancer cells -- EMT Epithelial to mesenchymal transition -- Th1/2 T helper type 1/2 -- CTCs Circulating tumor cells -- PR Progesterone receptor -- HER2 Human epidermal growth factor 2 -- RANKL Receptor activator of nuclear factor kappa-B ligand -- MAPK Mitogen-activated protein kinase -- ER Estrogen receptor -- RARβ Retinoic acid receptor beta -- HNSCC Head and neck squamous cell cancer -- NSCLC Non-squamous cell lung cancer -- VIM Vimentin -- ALDH1 Aldehyde dehydrogenase 1 -- CDK Cyclin-dependent kinase -- TSPAN8 tetraspanin -- EPS8 Epidermal growth factor receptor pathway substrate 8 -- GILZ Glucocorticoid-induced leucine zipper -- Zeb1/2 Zinc finger E-box-binding homeobox ½ -- PI3Kα Phosphoinositide 3-kinase alpha -- TNBC Triple negative breast cancer -- BM Bone marrow -- SDF1 Stromal cell-derived factor 1 -- CXCR4 C-X-C Motif Chemokine Receptor 4 -- AJ Adherins junctions -- mTOR Mammalian target of rapamycin -- ECM Extracellular matrix -- ASF Actin stress fibers -- MLCK Myosin light-chain kinase -- ERK Extracellular signal-regulated kinase -- BMP7 Bone morphogenetic protein 7 -- TGF-β Transforming growth factor beta -- CDK4 Cyclin-dependent kinase 4 -- STAT3 Signal transducer and activator of transcription 3 -- SOCS3 Suppressor of cytokine signaling 3 -- IFN Interferon -- TNF-α Tumor necrosis factor alpha -- IL Interleukin -- TAMS Tumor associated macrophages -- EGF/R Epidermal growth factor/receptor -- MDSC Myeloid-derived suppressor cells -- IRF7 Interferon regulatory transcription factor 7 -- VCAM-1 Vascular cell adhesion protein 1 -- T-DM1 Trastuzumab emtansine -- ADCC Antibody-dependent cellular cytotoxicity -- VEGF Vascular endothelial growth factor -- PD1 Programmed cell death protein 1 -- PD-L1 Programmed death-ligand 1 -- TLR Toll-like receptor -- STING Stimulator of interferon genes -- NK cells Natural killer cells -- hPMSA human prostate-specific membrane antigen -- TME tumor microenvironment -- SMI Small molecule inhibitor; Breast cancer -- Disseminated cancer cells -- Metastasis -- Th1 immune cells and immunotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2021.02.004
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Metastatic spread in breast cancer patients is the major driver of cancer-related deaths. A unique subset of cells disseminated from pre-invasive or primary tumor lesions are recognized as the main seeds for metastatic outgrowth. Disseminated cancer cells (DCCs) can migrate to distant organs and settle in a dormant state for a prolonged period until they emerge to overt metastases. Understanding the biology of breast cancer cells dissemination, dormancy and reactivation to form overt metastases has become an important focus. In this review, we discuss the recent advancements of molecular pathways involving breast cancer cell dissemination, role of chemokine-chemokine receptor networks in DCCs migration, DCCs phenotypic heterogeneity and unique genes signatures in tumor dormancy, microenvironmental regulation and specific niches that favors DCCs homing and dormancy. In addition, we also discuss recent findings relating to the role of immune response on DCC dissemination and dormancy. With recent advances in the field of immunotherapy/targeted therapy and its beneficial effects in cancer treatment, this review will focus on their impact on DCCs, reversal of stemness, tumor dormancy and metastatic relapse.