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Among patients with unresectable or metastatic esophageal cancer who receive definitive chemotherapy or chemoradiotherapy, the rates of treatment-related adverse events and incomplete treatment remain high. We conducted this study to investigate survival after definitive treatments and identify predicting factors for incomplete treatment. The data of patients who received definitive chemotherapy or chemoradiotherapy for esophageal cancer were retrospectively examined. The patients were assigned to Group 1: incomplete definitive treatment; Group 2: complete definitive treatment; or Group 3: complete definitive treatment with additional salvage surgery. The data of 273 patients (90, 166, and 17 in Groups 1, 2, and 3, respectively) were analyzed. In the survival analysis, the median overall survival of Groups 1, 2, and 3 were 2.6, 10.3, and 29.5 months, respectively. A significant difference in 3-year overall survival was observed among the groups (2.2%, 12.4%, and 48.5%, p < 0.001). In multivariable analysis, the independent risk factors for incomplete definitive treatment included poor performance score (hazard ratio (HR): 5.23, p = 0.001), bone metastasis (HR: 2.18, p = 0.024), airway invasion (HR: 2.90, p = 0.001), and liver cirrhosis (HR: 3.20, p = 0.026). Incomplete definitive treatment is associated with a far worse prognosis. Poor performance, bone metastasis, airway invasion, and liver cirrhosis are risk factors for incomplete treatment.

Background: Advances in surgical techniques and treatment modalities have improved the outcomes of esophageal cancer, yet difficult decision making for physicians while encountering multiple primary cancers (MPCs) continues to exist. The aim of this study was to evaluate long-term survival for esophageal squamous cell carcinoma (SCC) associated with MPCs. Methods: Data from 544 patients with esophageal SCC who underwent surgery between 2005 and 2017 were reviewed to identify the presence of simultaneous or metachronous primary cancers. The prognostic factors for overall survival (OS) were analyzed. Results: Three hundred and ninety-seven patients after curative esophagectomy were included, with a median observation time of 44.2 months (range 2.6−178.6 months). Out of 52 patients (13.1%) with antecedent/synchronous cancers and 296 patients without MPCs (control group), 49 patients (12.3%) developed subsequent cancers after surgery. The most common site of other primary cancers was the head and neck (69/101; 68.3%), which showed no inferiority in OS. Sex and advanced clinical stage (III/IV) were independent risk factors (p = 0.031 and p < 0.001, respectively). Conclusion: Once curative esophagectomy can be achieved, surgery should be selected as a potential therapeutic approach if indicated, even with antecedent/synchronous MPCs. Subsequent primary cancers were often observed in esophageal SCC, and optimal surveillance planning was recommended.

Background: The most beneficial neoadjuvant chemoradiotherapy (nCRT) combination for esophageal squamous cell carcinoma (ESCC) in Asia remains uncertain. Herein, we compared the neoadjuvant carboplatin/paclitaxel (CROSS) regimen versus the cisplatin/5-fluorouracil (PF) regimen in combination with 41.4-50.4 Gy of radiotherapy., Methods: Patients were stratified according to their nCRT regimen: CROSS + 41.4-45.0 Gy (CROSS), PF + 45.0 Gy (PF4500) or PF + 50.4 Gy (PF5040). Propensity score matching by inverse probability of treatment weighting (IPTW) was used to balance the baseline variables., Results: Before IPTW, a total of 334 patients were included. The lowest chemotherapy completion rate was observed in the PF5040 group (76.2% versus 89.4% and 92.0% in the remaining two groups, respectively). Compared with CROSS, both PF groups showed more severe weight loss during nCRT and a higher frequency of post-esophagectomy anastomotic leaks. The use of PF5040 was associated with the highest rate of pathological complete response (45.3%). While CROSS conferred a significant overall survival benefit over PF4500 (hazard ratio [HR] = 1.30, 95% CI = 1.05 to 1.62, p = 0.018), similar survival figures were observed when compared with PF5040 (HR = 1.17, 95% CI = 0.94 to 1.45, p = 0.166)., Conclusions: The CROSS regimen conferred a significant survival benefit over PF4500, although the similar survival figures were similar to those observed with PF5040. Considering the lower incidences of severe weight loss and post-esophagectomy anastomotic leaks, CROSS represents a safe and effective neoadjuvant treatment for Taiwanese patients with ESCC.

Circular RNAs (circRNAs) are noncoding products of backsplicing of pre-mRNAs which have been established to possess potent biological functions. Dysregulated circRNA expression has been linked to diseases including different types of cancer. Cancer progression is known to result from the dysregulation of several molecular mechanisms responsible for the maintenance of cellular and tissue homeostasis. The dysregulation of these processes is defined as cancer hallmarks, and the molecular pathways implicated in them are regarded as the targets of therapeutic interference. In this review, we summarize the literature on the investigation of circRNAs implicated in cancer hallmark molecular signaling. First, we present general information on the properties of circRNAs, such as their biogenesis and degradation mechanisms, as well as their basic molecular functions. Subsequently, we summarize the roles of circRNAs in the framework of each cancer hallmark and finally discuss the potential as therapeutic targets.

Peptide drugs that target protein-protein interactions have attracted mounting research efforts towards clinical developments over the past decades. Increasing reports have indicated that expression of Musashi 1 (MSI1) is tightly correlated to high grade of cancers as well as enrichment of cancer stem cells. Treatment failure in malignant tumors glioblastoma multiform (GBM) had also been correlated to CSC-regulating properties of MSI1. It is thus imperative to develop new therapeutics that could effectively improve current regimens used in clinics. MSI1 and AGO2 are two emerging oncogenic molecules that both contribute to GBM tumorigenesis through mRNA regulation of targets involved in apoptosis and cell cycle. In this study, we designed peptide arrays covering the C-terminus of MSI1 and identified two peptides (Pep#11 and Pep#26) that could specifically interfere with the binding with AGO2. Our Biacore analyses ascertained binding between the identified peptides and AGO2. Recombinant reporter system Gaussian luciferase and fluorescent bioconjugate techniques were employed to determine biological functions and pharmacokinetic characteristics of these two peptides. Our data suggested that Pep#11 and Pep#26 could function as decoy peptides by mimicking the interaction function of MSI1 with its binding partner AGO2 in vitro and in vivo. Further experiments using GMB animal models corroborated the ability of Pep#11 and Pep#26 in disrupting MSI1/AGO2 interaction and consequently anti-tumorigenicity and prolonged survival rates. These striking therapeutic efficacies orchestrated by the synthetic peptides were attributed to the decoy function to C-terminal MSI1, especially in malignant brain tumors and glioblastoma.