Owing to the limitations of the present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of the understanding of the biological regulation mechanisms underlying COVID-19, alternative or novel therapeutic targets for COVID-19 treatment are still urgently required. SARS-CoV-2 infection and immunity dysfunction are the two main courses driving the pathogenesis of COVID-19. Both the virus and host factors are potential targets for antiviral therapy. Hence, in this study, the current therapeutic strategies of COVID-19 have been classified into “target virus” and “target host” categories. Repurposing drugs, emerging approaches, and promising potential targets are the implementations of the above two strategies. First, a comprehensive review of the highly acclaimed old drugs was performed according to evidence-based medicine to provide recommendations for clinicians. Additionally, their unavailability in the fight against COVID-19 was analyzed. Next, a profound analysis of the emerging approaches was conducted, particularly all licensed vaccines and monoclonal antibodies (mAbs) enrolled in clinical trials against primary SARS-CoV-2 and mutant strains. Furthermore, the pros and cons of the present licensed vaccines were compared from different perspectives. Finally, the most promising potential targets were reviewed, and the update of the progress of treatments has been summarized based on these reviews.
Immunotherapy that includes programmed cell death-1 (PD-1), programmed cell death- ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors has revolutionized the therapeutic strategy in multiple malignancies. Although it has achieved significant breakthrough in advanced non-small cell lung cancer patients, immune-related adverse events (irAEs) including checkpoint inhibitor pneumonitis (CIP), are widely reported. As the particularly worrisome and potentially lethal form of irAEs, CIP should be attached more importance. Especially in non-small cell lung cancer (NSCLC) patients, the features of CIP may be more complicated on account of the overlapping respiratory signs compromised by primary tumor following immunotherapy. Herein, we included the previous relevant reports and comprehensively summarized the characteristics, diagnosis, and management of CIP. We also discussed the future direction of optimal steroid therapeutic schedule for patients with CIP in NSCLC based on the current evidence.
Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.
Background Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) was a sparse subtype of unclassified lung cancer. The clinicopathologic features, prognostic factors and multimodality treatment regimens of LELC remain inconclusive. We conducted this systematic review and meta-analysis to address this deficit in current knowledge. Methods We searched PubMed, Embase, and Web of Science to filtrate studies investigating on clinical features and prognostic factors of LELC up to Sep 9 th , 2020. Fixed and random effect models were generated to present the incorporated hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI). The quality and heterogeneity of the included studies were also evaluated carefully. Results This systematic review and meta-analysis included 13 retrospective studies with a total of 1294 patients. The incidence of programmed cell death-ligand 1 (PD-L1) expression in PPLELC varied from 63.3% to 75.8%. Positive PD-L1 expression was more likely to be found in patients under 60 years old (OR = 2.16, 95%CI: 1.19-3.89, P = 0.01) and was associated with worse disease-free survival (DFS) compared with negative PD-L1 expression (HR = 2.99, 95%CI: 1.23-7.28, P = 0.02). The pooled results showed that stage was the prognostic factor for both overall survival (OS) and DFS. Moreover, a significantly better outcome of PPLELC was observed in men (HR = 0.56, 95%CI: 0.33-0.95, P = 0.03) and patients who received radiation (HR = 0.46, 95%CI: 0.22-0.96, P = 0.04).
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