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Galectin-1, a novel promising target for outcome prediction and treatment in SCLC

Introduction: small-cell lung cancer (SCLC) is one of the most lethal malignancies. Its management is complex due to the lack of biomarkers and limited therapies. Galectin-1 (Gal-1) plays a major role in cancer development and progression. The aim of this study is to assess whether Gal-1 has a predictive role in the disease evolution and its therapeutic potential.

Material and methods: The expression level of Gal-1 was examined by using a public RNA-sequencing (77 SCLC patients) and in-house immunohistochemistry (IHC) performed on biopsies from 81 patients. Survival curves and Cox regression analysis were used to assess the prognostic potential of Gal-1. In addition, a SCLC-PDX model was carried out and treated with either OTX008, an inhibitor of Gal-1, or vehicle to assess the effects of Gal-1 inhibition on this disease in vivo.

Results: Galectin-1 gene (LGALS1) expression showed a strong negative correlation with outcome in SCLC patients with advanced disease (p = 0.007). IHC unveiled that overall survival (OS) was significantly lower among extensive-stage SCLC (ES-SCLC) patient group with increased level of Gal-1 and platelet-to-lymphocyte ratio (PLR) (HR=3.07, 95% CI: 1.62, 5.79, p < 0.001). The SCLC-PDX model showed a significant reduction in tumor size (tumor growth inhibition [TGI] index 73%) without side effects.

Discussion: in this study, high levels of Gal-1 and PLR were associated with poorer OS in SCLC patients, supporting their utility as clinical prognostic biomarkers. Moreover, the in vivo model suggests the inhibition of Gal-1 as a novel potential therapy for this disease with very poor prognosis.

Comments：

It appears that Gal-1 may play a significant role in SCLC development and progression. The study utilized both RNA-sequencing and immunohistochemistry to assess Gal-1 expression in SCLC patients. The results indicated that high levels of Gal-1 and platelet-to-lymphocyte ratio (PLR) were associated with poor overall survival in patients with advanced disease.

In addition, the study utilized a SCLC-PDX model to assess the effects of Gal-1 inhibition on tumor growth in vivo. The results showed a significant reduction in tumor size without any observed side effects, suggesting the inhibition of Gal-1 as a potential therapy for SCLC.

Overall, this study provides important insights into the potential utility of Gal-1 as a prognostic biomarker and therapeutic target in SCLC. Further research in this area could lead to improved outcomes for patients with this challenging malignancy.

Related Products

Cat.No. Product Name Information
S6949 OTX008 OTX008 (Calixarene 0118, PTX008), a calixarene derivative, is a selective inhibitor of galectin-1 (Gal1) with anti-tumoural activity.

Related Targets

Galectin