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Gastrointestinal cancer stem cells as targets for innovative immunotherapy.

ABSTRACT: The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells (GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies, recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system. Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio- or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.

SUBMITTER: Chivu-Economescu M

PROVIDER: S-EPMC7167409 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Gastrointestinal cancer stem cells as targets for innovative immunotherapy.

Chivu-Economescu Mihaela M Necula Laura G LG Matei Lilia L Dragu Denisa Laura DL Neagu Ana I AI Alexiu Irina I Bleotu Coralia C Diaconu Carmen Cristina CC

World journal of gastroenterology 20200401 14

The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells (GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies, recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have ...[more]

PMID: 32327907

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Project description:Breast cancer stem cells (BCSCs) play a critical role in chemoresistance, metastasis, and poor prognosis of breast cancer. BCSCs are mostly dormant, and therefore, activating them and modulating the cell cycle are important for successful therapy against BCSCs. The tumor microenvironment (TME) promotes BCSC survival and cancer progression, and targeting the TME can aid in successful immunotherapy. Honokiol (HNK), a bioactive polyphenol isolated from the bark and seed pods of Magnolia spp., is known to exert anticancer effects, such as inducing cell cycle arrest, inhibiting metastasis, and overcoming immunotherapy resistance in breast cancer cells. However, the molecular mechanisms of action of HNK in BCSCs, as well as its effects on the cell cycle, remain unclear. This study aimed to explore the potential targets and molecular mechanisms of HNK on metastatic BCSC (mBCSC)-cell cycle arrest and the impact of the TME. Using bioinformatics analyses, we predicted HNK protein targets from several databases and retrieved the genes differentially expressed in mBCSCs from the GEO database. The intersection between the differentially expressed genes (DEGs) and the HNK-targets was determined using a Venn diagram, and the results were analyzed using a protein-protein interaction network, hub gene selection, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, genetic alteration analysis, survival rate, and immune cell infiltration levels. Finally, the interaction between HNK and two HNK-targets regulating the cell cycle was analyzed using molecular docking analysis. The identified potential therapeutic targets of HNK (PTTH) included CCND1, SIRT2, AURKB, VEGFA, HDAC1, CASP9, HSP90AA1, and HSP90AB1, which can potentially inhibit the cell cycle of mBCSCs. Moreover, our results showed that PTTH could modulate the PI3K/Akt/mTOR and HIF1/NFkB/pathways. Overall, these findings highlight the potential of HNK as an immunotherapeutic agent for mBCSCs by modulating the tumor immune environment.

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Gastrointestinal cancer stem cells as targets for innovative immunotherapy.

Publications

Gastrointestinal cancer stem cells as targets for innovative immunotherapy.

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