MicroRNAs (miRNAs) are attractive therapeutic targets and promising candidates as molecular biomarkers for various therapy-resistant tumors. However, the association between miRNAs and drug resistance in melanoma remains to be elucidated. We used an integrative genomic analysis to comprehensively study the miRNA expression profiles of drug-resistant melanoma patients and cell lines. MicroRNA-181a and -181b (miR181a/b) were identified as the most significantly down-regulated miRNAs in resistant melanoma patients and cell lines. Re-establishment of miR-181a/b expression reverses the resistance of melanoma cells to the BRAF inhibitor dabrafenib. Introduction of miR-181 mimics markedly decreases the expression of TFAM in A375 melanoma cells resistant to BRAF inhibitors. Furthermore, melanoma growth was inhibited in A375 and M14 resistant melanoma cells transfected with miR-181a/b mimics, while miR-181a/b depletion enhanced resistance in sensitive cell lines. Collectively, our study demonstrated that miR-181a/b could reverse the resistance to BRAF inhibitors in dabrafenib resistant melanoma cell lines. In addition, miR-181a and -181b are strongly down-regulated in tumor samples from patients before and after the development of resistance to targeted therapies. Finally, melanoma tissues with high miR-181a and -181b expression presented favorable outcomes in terms of Progression Free Survival, suggesting that miR-181 is a clinically relevant candidate for therapeutic development or biomarker-based therapy selection.

Bile-duct cancers (BDC) are a group of solid tumors arising from the biliary tree. Despite their classification as rare cancers, the incidence of BDC is increasing worldwide. Poor prognosis is a common feature of this type of cancer and is mainly determined by the following factors: late diagnosis, lack of effective therapeutic approaches, and resistance to conventional treatments. In the past few years, next-generation sequencing technologies has allowed us to study the genome, exome, and transcriptome of BDC deeper, revealing a previously underestimated class of RNA: the noncoding RNA (ncRNA). MicroRNAs (miRNAs) are small ncRNAs that play an important regulatory role in gene expression. The aberrant expression of miRNAs and their pivotal role as oncogenes or tumor suppressors in biliary carcinogenesis has been widely described in BDC. Due to their ability to regulate multiple gene networks, miRNAs are involved in all cancer hallmarks, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism, and avoiding immune destruction. Their use as diagnostic, prognostic, and predictive biomarkers has been widely explored in several human cancers, including BDC. Furthermore, miRNA-based therapeutic strategies are currently the subject of numerous clinical trials that are providing evidence of their efficacy as potent anticancer agents. In this review, we will provide a detailed update of miRNAs affecting BDC, discussing their regulatory function in processes underlying the molecular pathology of BDC. Finally, an overview of their potential use as biomarkers or therapeutic tools in BDC will be further addressed.

Background: Few data about the link between nutritional status and survival are available in the metastatic gastric cancer (GC) setting. The aim of this work was to evaluate the prognostic role of tissue modifications during treatment and the benefit of a scheduled nutritional assessment in this setting. Methods: Clinical and laboratory variables of 40 metastatic GC patients treated at Modena Cancer Center were retrieved: 20 received a nutritional assessment on the oncology’s discretion, the other 20 received a scheduled nutritional assessment at baseline and every 2–4 weeks. Anthropometric parameters were calculated on Computed Tomography (CT) images at the baseline and after 3 months of chemotherapy. Results: A correlation between baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS), Lymphocyte to Monocyte Ratio (LMR), C-reactive protein (PCR), Prognostic Nutritional Index (PNI) and Overall survival (OS) was highlighted. Among the anthropometric parameters, early skeletal muscle mass depletion (ESMMD) >10% in the first months of treatment significantly impacted on mOS (p = 0.0023). A link between ESMMD and baseline LDH > 460 U/L, baseline CRP > 2.2 mg/dL and weight decrease during treatment emerged. Patients evaluated with a nutritional scheduled support experienced a mean gain in subcutaneous and visceral fat of 11.4% and 10.21%, respectively. Conclusion: We confirm the prognostic impact of ESMMD > 10% during chemotherapy in metastatic GC. The prognostic role of a scheduled nutritional assessment deserves further confirmation in large prospective trials.