Oncology research and treatment
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Hepatocellular carcinoma (HCC) is one of the most deadly and rapidly evolving cancers worldwide. The current systemic treatment strategies in advanced tumor stages remain limited despite promising preclinical and early-phase clinical results for some compounds, highlighting an unmet clinical need. ⋯ Besides oncolytic viruses, vaccines, or immune cell infusions, first results from early-phase clinical trials particularly encourage the use of immune checkpoint inhibitors against PD-1/PD-L1 and CTLA-4 for HCC. In this review, we delineate the current clinical and preclinical landscape of immunotherapies in HCC, critically discuss recent findings from clinical trials and outline future perspectives in the field of liver cancer.
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Meta Analysis
Prognostic Value of miR-375 for Survival Outcomes in Various Cancers: A Systematic Review and Meta-Analysis.
miR-375 plays a role in tumor progression; however, its potential as a prognostic factor in cancer remains unclear. This meta-analysis assessed the value of miR-375 as a global prognostic biomarker in human cancer. ⋯ Low miR-375 expression could represent a valuable prognostic marker in various cancers. Circulating miR-375 levels may provide a useful non-invasive, practical prognostic biomarker. However, the prognostic value of miR-375 in specific cancer types remains unclear; further studies are warranted.
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Immune checkpoint inhibitors are emerging as a therapeutic approach for patients with advanced or metastatic gastrointestinal malignancies following the recent Food and Drug Administration and Asian approvals for colorectal, gastric, and hepatocellular carcinoma. As discussed in earlier articles, phase I-II trials demonstrate quite positive clinical activity, particularly in patients with immunogenic cancer subtypes. ⋯ Here, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells are increasingly coming into focus as new targets. Besides the well described use of checkpoint inhibitors, blockade of 'Wnt' or Csf1R signaling pathways as well as combinatorial treatment strategies offer promising examples for overcoming immune silencing within the resistant tumor microenvironment.
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In contrast to other tumour types inhibitors of PD-1/-L1 or CTLA 4 have not yet shown relevant efficacy in unselected colorectal cancer. Based on the high mutational burden, deficient mismatch repair (dMMR) or microsatellite instable (MSI-H) tumours are yet the only subgroup, which is amenable to checkpoint inhibition. ⋯ For the by far larger subgroup of non-dMMR/MSI-H patients (95% in the metastatic setting) combination regimen are urgently required, either with chemotherapy and/or molecular targeting drugs, local ablative treatments or other immunotherapeutic agents (e.g. CEA-TCB).