Cancer letters
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Machine learning (ML) is a branch of artificial intelligence centered on algorithms which do not need explicit prior programming to function but automatically learn from available data, creating decision models to complete tasks. ML-based tools have numerous promising applications in several fields of medicine. ⋯ For instance, they have been employed for oncological risk assessment, automated segmentation, lesion detection, characterization, grading and staging, prediction of prognosis and therapy response. In the near future, ML could become essential part of every step of oncological screening strategies and patients' management thus leading to precision medicine.
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Immune checkpoint inhibitors against PD-1/PD-L1 yield improved survival rates of KRAS-mutant NSCLC patients, who conferred a poor prognosis without effective targeted therapy until now. Yet, the underlying association between KRAS mutations and immune responses remains unclear. We performed an integrated analysis of the data from publicly available repositories and from clinical center cohorts to explore the association between KRAS mutation status and tumor immunity-associated features, including PD-L1 expression, CD8+ tumor-infiltrating lymphocytes (TILs) and tumor mutational burden (TMB). ⋯ In addition, a KRAS-mutant lung adenocarcinoma mouse model was established to estimate the relative efficacy of anti-PD-L1 monoclonal antibody monotherapy or combination treatment with docetaxel versus docetaxel alone. Most surprisingly, we found that PD-L1 blockade combined with docetaxel did not promote an anti-tumor response. These findings uncover that PD-1/PD-L1 blockade monotherapy may be the optimal therapeutic schedule in NSCLC patients harboring KRAS mutations.
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Oesophago-gastric cancers (OGCs) are aggressive tumours. While better peri-operative strategies, increased number of cytotoxic agents and availability of targeted therapies have improved survival, there remains an unmet need for novel treatment approaches. Immune checkpoint inhibitors (ICIs) have marked a new era in cancer management with unprecedented results in several malignancies. ⋯ Furthermore, studies are evaluating ICIs in the early stage setting and exploring the potential of combination treatments. In this article we discuss the biological bases underlying the successful development of ICIs in OGC and review the available data on PD-1 and PD-L1 monoclonal antibodies in this disease. Also, we present ongoing clinical trials of these ICIs that could shape the future treatment landscape of OGC.
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Gut microbiota dysbiosis is closely involved in intestinal carcinogenesis. A marked reduction in butyrate-producing bacteria has been observed in patients with colorectal cancer (CRC); nevertheless, the potential benefit of butyrate-producing bacteria against intestinal tumor development has not been fully investigated. We found that Clostridium butyricum (C. butyricum, one of the commonly used butyrate-producing bacteria in clinical settings) significantly inhibited high-fat diet (HFD)-induced intestinal tumor development in Apcmin/+ mice. ⋯ The anti-proliferative effect of C. butyricum was blunted by GPR43 gene silencing using small interfering RNA (siRNA). The analysis of clinical specimens revealed that the expression of GPR43 and GPR109A gradually decreased from human normal colonic tissue to adenoma to carcinoma. Together, our results show that C. butyricum can inhibit intestinal tumor development by modulating Wnt signaling and gut microbiota and thus suggest the potential efficacy of butyrate-producing bacteria against CRC.
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Accumulating evidence indicates that CCL18 and the long non-coding RNA, HOTAIR, have critical roles in cancer progression and metastasis, but the correlation between CCL18 and HOTAIR in esophageal squamous cell carcinoma (ESCC) and their downstream molecular mechanisms remain unclear. Overexpression of CCL18 in ESCC tissues was associated with a worse survival in patients with ESCC. CCL18 enhanced the invasiveness of ESCC cells in a dose-dependent manner, whereas CCL18 knockdown inhibited their invasiveness. ⋯ Our study suggests that CCL18 contributes to the malignant progression of esophageal cancer by upregulating HOTAIR expression. HOTAIR overexpression may promote tumor invasiveness and progression in ESCC, given that HOTAIR functions as a miR-130a-5p sponge, positively regulating ZEB1. This provides new therapeutic targets for early diagnosis and treatment of ESCC.