Drug Repurposing for Targeting Myeloid-Derived Suppressor-Cell-Generated Immunosuppression in Ovarian Cancer: A Literature Review of Potential Candidates

Author:

Berckmans Yani1ORCID,Hoffert Yannick2ORCID,Vankerckhoven Ann1ORCID,Dreesen Erwin2ORCID,Coosemans An1ORCID

Affiliation:

1. Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, Katholieke Universiteit Leuven, 3000 Leuven, Belgium

2. Clinical Pharmacology and Pharmacotherapy Unit, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, 3000 Leuven, Belgium

Abstract

The lethality of patients with ovarian cancer (OC) remains high. Current treatment strategies often do not lead to the desired outcome due to the development of therapy resistance, resulting in high relapse rates. Additionally, clinical trials testing immunotherapy against OC have failed to reach significant results to date. The OC tumor microenvironment and specifically myeloid-derived suppressor cells (MDSC) are known to generate immunosuppression and inhibit the anti-tumor immune response following immunotherapy treatment. Our review aims to characterize potential candidate treatments to target MDSC in OC through drug-repurposing. A literature search identified repurposable compounds with evidence of their suppressing the effect of MDSC. A total of seventeen compounds were withheld, of which four were considered the most promising. Lurbinectedin, metformin, celecoxib, and 5-azacytidine have reported preclinical effects on MDSC and clinical evidence in OC. They have all been approved for a different indication, characterizing them as the most promising candidates for repurposing to treat patients with OC.

Publisher

MDPI AG

Subject

Pharmaceutical Science

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