Therapeutic opportunities for PLK1 inhibitors: Spotlight on BRCA1-deficiency and triple negative breast cancers

GARCÍA, IRIS ALEJANDRA; GARRO, CINTIA; FERNANDEZ, ELMER; SORIA, GASTÓN

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS

ELSEVIER SCIENCE BV

Año: 2020 vol. 821

0027-5107

olo-Like Kinases (PLKs) are central players of mitotic progression in Eukaryotes. Given the intimate relationship between cell cycle progression and cancer development, PLKs in general and PLK1 in particular have been thoroughly studied as biomarkers and potential therapeutic targets in oncology. The oncogenic properties of PLK1 overexpression across different types of human cancers are attributed to its roles in promoting mitotic entry, centrosome maturation, spindle assembly and cytokinesis. While several academic labs and pharmaceutical companies were able to develop potent and selective inhibitors of PLK1 (PLK1i) for preclinical research, such compounds have reached only limited success in clinical trials despite their great pharmacokinetics. Even though this could be attributed to multiple causes, the housekeeping roles of PLK1 in both normal and cancer cells are most likely the main reason for clinical trials failure and withdraw due to toxicities issues. Therefore, great effort