2016P - The role of galectin-1 in SCLC: Prognostic significance and therapeutic implications

Background

Not much has changed in the SCLC landscape over the past 40 years, apart from the addition of checkpoint inhibitors, which have been the most notable advance in clinical management since the 1980s. As a result, greater efforts are needed to develop more therapies to combat this type of cancer. Galectin-1 (Gal-1) has emerged as an interesting player due to its involvement in crucial roles in cancer development. Our objective was to assess whether Gal-1 has a prognostic role in SCLC outcomes and its potential for use in both monotherapy and combination with platinum-based therapy.

Methods

We analyzed Gal-1 expression in 77 SCLC patients using RNA sequencing and in 81 patients using in-house immunohistochemistry (IHC). We evaluated the prognostic potential of Gal-1 using survival curves and Cox regression analysis. Additionally, we established a SCLC-PDX model and randomized it into four groups to assess the effects of Gal-1 inhibition in monotherapy and in combination with platinum-based therapy. To evaluate antitumor activity, T/C ratio was applied.

Results

Galectin-1 gene (LGALS1) expression showed a strong negative correlation with outcomes in SCLC patients with advanced disease (p = 0.007). Furthermore, IHC analysis revealed that in patients with advanced disease, a high Gal-1 score (Gal-1 score >3) and high Platelets to Lymphocytes Ratio (PLR > 186) as a combined variable presented a HR=3.07, 95% CI: 1.62, 5.79, p < 0.001, with a significant impact on survival (median time (weeks) for OS was 31 in the high/high group versus 41.1 in the other group). The SCLC-PDX model showed a significant reduction in tumor growth in both the OTX008 (T/C 66%) and carboplatin/etoposide (T/C 65%) groups, with the greatest effect attributable to the combination (T/C 46%).

Conclusions

Our findings suggest that high levels of Gal-1 and PLR are associated with poorer OS in SCLC patients and can be useful as clinical prognostic biomarkers. Moreover, our in vivo model suggests that the inhibition of Gal-1 could be a novel potential therapy with a significant impact in combination with platinum-based therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Instituto de Investigación Sanitaria Fundación Jiménez Díaz.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.