Novel Class of Galectin 1 Inhibitors for Prostate Cancer Therapy
Non-conventional in English | NTIS | ID: grc-753746
ABSTRACTThe overall goal of this award is to find ways to prolong the efficacy of cabazitaxel chemotherapy in patients with castration resistant prostate cancer (CRPC) who have previously been treated with and developed resistance to Abiraterone Acetate (ABI) or enzalutamide (ENZ). In months 1-12 of this award, we aimed to determine whether a novel galectin-1 (Gal-1) inhibitor, S-LLS30 developed by the applicant, prevents ABI/ENZ resistance and/or sensitizes the cells to cabazitaxel (Major task 1). We have shown that indeed S-LLS30 sensitizes CRPC cells to ENZ and strongly affected cells expressing Gal-1. The experiments with cabazitaxel are continuing despite prolonged operational shutdown at the University due to COVID-19 restrictions. We have also started to investigate the role of Gal-1 nuclear localization, and its binding partners Gemin4 and HSP90 in this process (Major task 2, subtask 1). It appears that Gemin4 plays a substantial role in Gal-1 activity in this context but the role of HSP90 is unclear. Finally, we conducted preliminary experiments to evaluate the toxicity of S-LLS30 and determine the maximum tolerated dose (Major task 3, subtask 1). S-LLS30 was deemed to be of limited toxicity and very well tolerated in mice up to 30 mg/Kg doses. S-LLS30 is a viable potential drug candidate to overcome resistance to ABI/ENZ in models of CRPC.
Full text: Available Collection: Databases of international organizations Database: NTIS Type of study: Experimental Studies Language: English Year: 2020 Document Type: Non-conventional