The aim of this study was to evaluate the efficacy and safety of afatinib combined with oral metronomic vinorelbine as a second-line treatment for patients with advanced lung squamous cell carcinoma (LSCC). A retrospective analysis was conducted on 38 patients with advanced LSCC who had failed first-line platinum-based doublet chemotherapy combined with immunotherapy between January 2022 and June 2024. All patients received afatinib (30 mg or 40 mg orally once daily) combined with oral metronomic vinorelbine (20 mg or 30 mg orally three times weekly on Monday, Wednesday, and Friday) until disease progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs). Based on the data, the ORR was 26.3%, and the DCR was 68.4%. The median PFS was 5.0 months (95% CI: 4.7-5.4), and the median OS was 9.0 months (95% CI: 8.6-10.0). Grade ≥3 TRAEs occurred in 23.7% (9/38) of patients, including diarrhea (5.3%), rash (5.3%), neutropenia (5.3%), stomatitis (2.6%), and fatigue (2.6%). No grade 4-5 TRAEs or treatment-related deaths occurred. To conclude, the combination of afatinib and oral metronomic vinorelbine demonstrates promising antitumor activity and a manageable safety profile as a second-line treatment for advanced LSCC. This combo could represent an option as second-line after failure of chemo+IO.
Wilms' tumor (WT) represents a kidney carcinoma predominantly affecting children aged five years and younger. Heterogeneous nuclear ribonucleoprotein D (hnRNPD), an RNA-binding protein, has been implicated in oncogenic processes across various tumor types, whereas its expression pattern and biological function in WT remain largely unknown. hnRNPD expression within WT tissues was evaluated using publicly available databases, and co-expressed genes were identified through bioinformatic analysis. In vitro, hnRNPD expression in WT cell lines 17.94 and HFWT was modulated via gene silencing or overexpression. We subsequently carried out functional assays to assess cell proliferation and apoptosis. Molecular experiments were conducted to determine p38 mitogen-activated protein kinase (p38 MAPK) pathway activation status within cells with altered hnRNPD expression. Furthermore, SB203580 was utilized to pharmacologically inhibit this pathway to investigate the mechanism of hnRNPD in regulating WT cell proliferation. Data showed that hnRNPD was upregulated in WT tissues and cells. Silencing hnRNPD significantly inhibited WT cell proliferation and promoted apoptosis. Conversely, overexpression of hnRNPD produced the opposing effects. MAPK14, the gene encoding the p38α isoform of p38 MAPK, was identified as a core gene within the hnRNPD co-expression network. Furthermore, the phosphorylation level of p38 MAPK in WT cells was markedly elevated compared to that in normal cells. However, inhibition of the p38 MAPK pathway using SB203580 suppressed WT cell proliferation. Notably, SB203580 effectively counteracted the pro-proliferative effect of hnRNPD overexpression on malignant WT cell growth. In conclusion, hnRNPD is highly expressed in WT and plays a significant role in promoting the malignant proliferation of WT cells. The underlying molecular mechanism involves the regulation of p38 MAPK signaling pathway activation.
In a recent study, the exogenous administration of angiotensin 1-7 (Ang 1,7) together with melatonin, 5-methoxytryptamine, and cannabidiol increased 1-year survival in advanced cancer patients, underlining the utility of neuromodulation in oncology. We now report a single-arm interventional study to evaluate the effectiveness of introducing Ang 1-7 in the neuroimmune regime, including pineal indoles and cannabinoids. Two cohorts of patients with advanced solid tumors refractory to standard oncologic treatments and with an estimated life expectancy of less than six months were studied. The full neuroimmune regimen cohort consisted of 100 consecutive patients treated over the last three years with Ang 1-7, pineal indoles, and cannabinoids, while the comparator cohort included 212 consecutive patients treated between 2015 and 2019 with pineal indoles and cannabinoids alone. Gastroprotected capsules of Ang 1-7 coupled with cyclodextrin were administered at 0.5 mg p.o. twice/day. Melatonin (100 mg) and 5-methoxytryptamine (20 mg) were given p.o. at bedtime and in the early afternoon, respectively. Cannabidiol or cannabigerol (in the case of glioblastoma) was given at 20 mg p.o. twice/day. Clinical response, disease control, and overall survival, along with the lymphocyte-to-monocyte ratio, were evaluated. In the full regimen cohort, disease control was achieved in 67 of 100 patients, with objective tumor regression observed in 23%. In the comparator cohort, disease control was obtained in 111 of 212 patients, with objective regression in 8%. Three-year overall survival was significantly higher in the full regimen cohort (37%) compared with the comparator cohort (19%). Both treatments were associated with a significant increase in the lymphocyte-to-monocyte ratio, suggesting an improvement in systemic immune status. The addition of Ang 1-7 to a neuroimmune regimen combining pineal indoles and cannabinoids was associated with improved disease control and long-term survival in patients with end-stage solid tumors lacking effective therapeutic options.
