Background Shenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has the good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea. Methods 24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80 mg/kg/qd pyrotinib) and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea. Results In vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the pyrotinib + SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, the network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection and cAMP signaling pathway. Conclusions SBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process.
Background: Immune checkpoint inhibitors (ICIs) are widely used for treating advanced non-small cell lung cancer (NSCLC). However, some studies indicate that patients with genetic mutations do not benefit from immunotherapy. Hence, this study explored the efficacy of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) antibodies in the first-line treatment of advanced NSCLC with driver gene mutations in real-world settings. Methods: We retrospective analyzed patients with advanced NSCLC who treated with first-line anti-PD-1/PD-L1 antibodies at Shandong Provincial Hospital between May 2019 and October 2020. The patient's driver gene mutation status was identified using amplification refractory mutation system PCR (ARMS-PCR). The basic clinical characteristics, objective response rate (ORR), progression free survival (PFS), and other clinical data of patients were collected to evaluate the clinical efficacy and potential prognostic factors of treatment for patients with driver gene mutations. Results: A total of 430 patients' information was counted during this period, finally, 89 patients with NSCLC were enrolled in the study. The main pathological subtype of patients was adenocarcinoma (62.9%). The overall mutation rate was 44.9% (n = 40) and included following mutations: KRAS (n = 20), TP53 (n = 18), EGFR (n = 6), BRAF (n = 3), Her-2 (n = 3), MET (n = 3), ROS1 (n = 1), and NRAS (n = 1). The overall ORR was 44.30% and the disease control rate (DCR) was 82.23%. At the time of follow-up cut-off, the median PFS of all patients was 8.2 month. In NSCLC patients treated with ICI, median PFS was longer in mutation-negative patients than in mutation-positive patients (8.98 vs 7.07 months, P < 0.05). Survival benefit varied across mutational subgroups: KRAS patients could benefit from first-line immunotherapy (10.1 months, P < 0.05), patients with EGFR mutations have poor first-line immunotherapy outcomes, with a median PFS of only 3.0 months (P < 0.01), and patients with other mutation types having no significant difference in response from mutation-negative patients. In most mutation subgroups, immune combination therapy had longer PFS than immune monotherapy, and PD-L1 expression levels were positively correlated with clinical benefit in patients. Conclusion:In the real world, patients with KRAS mutations benefit from first-line immunotherapy, immune-combination modalities are more effective, and immune efficacy is positively correlated with PD-L1 expression; Patients with other driver mutations (BRAF, NRAS, Her2, MET, ROS1) benefit similarly to mutation-negative patients in first-line immunotherapy, and immunotherapy is recommended for first-line therapy; Immunotherapy is worse effective in patients with EGFR mutations, immunotherapy is not recommended in first-line therapy even patients with high PD-L1 expression.
Small‐cell lung cancer (SCLC) accounts for 15%–20% of primary lung cancers, and it is characterized by low differentiation, rapid proliferation, and early metastasis. At least two‐thirds of SCLC patients present with the extensive stage (ES) at the time of initial clinical diagnosis. Over the last 2 decades, platinum‐based combination chemotherapy has remained the standard first‐line treatment for SCLC. With the introduction of the immunotherapy era, immunotherapy plus chemotherapy has replaced conventional chemotherapy as the first‐line treatment option for ES‐SCLC and is recommended by National Comprehensive Cancer Network clinical guidelines. Therefore, in this review, we present the latest research advances in SCLC treatment, predictive biomarkers, and other topics of high interest to provide options for patients with SCLC.
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