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Background: Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection. Methods: Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15. Results: There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42–2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26–1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46–0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61–13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24–0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46–0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34–5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients. Conclusions: The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection. [ABSTRACT FROM AUTHOR]

Intrinsically disordered proteins (IDPs) do not have a well-defined structure under physiological conditions, but they have key roles in cell signaling and regulation, and they are frequently related to the development of diseases, such as cancer and other malignancies. This has converted IDPs in attractive therapeutic targets; however, targeting IDPs is challenging because of their dynamic nature. In the last years, different experimental and computational approaches, as well as the combination of both, have been explored to identify molecules to target either the hot-spots or the allosteric sites of IDPs. In this review, we summarize recent developments in successful targeting of IDPs, all of which are involved in different cancer types. The strategies used to develop and design (or in one particular example, to repurpose) small molecules targeting IDPs are, in a global sense, similar to those used in well-folded proteins: (1) screening of chemically diverse or target-oriented compound libraries; or (2) study of the interfaces involved in recognition of their natural partners, and design of molecular candidates capable of binding to such binding interface. We describe the outcomes of using these approaches in targeting IDPs involved in cancer, in the view to providing insight, to target IDPs in general. In a broad sense, the designed small molecules seem to target the most hydrophobic regions of the IDPs, hampering macromolecule (DNA or protein)–IDP interactions; furthermore, in most of the molecule–IDP complexes described so far, the protein remains disordered. [ABSTRACT FROM AUTHOR]