Exploring the Impact of Pan-AURKs and Selective AURKB Inhibitors on Non-Small Cell Lung Cancer


Sarı S., Ozsoy E. R.

6th International Eurasian Conference on Biological and Chemical Sciences, Ankara, Turkey, 11 - 13 October 2023, pp.131

  • Publication Type: Conference Paper / Summary Text
  • City: Ankara
  • Country: Turkey
  • Page Numbers: pp.131
  • Abdullah Gül University Affiliated: Yes

Abstract

Aurora Kinase B (AURKB) is a mitotic serine/threonine protein kinase belonging to the highly conserved Aurora Kinase family of mitotic kinases, along with Aurora Kinase A and Aurora Kinase C. AURKB is a kinase module of the Chromosomal Passenger Complex, which plays critical roles in the cell cycle, including chromosome compaction and segregation, the spindle-assembly checkpoint and cytokinesis. While AURKB is ubiquitously expressed in healthy cells, it is overexpressed in various human cancers, including lung cancer. Lung cancer is the leading cause of global cancer mortality and incidence, with approximately 2.2 million diagnoses and 1.8 million deaths. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80-85% of all cases. In NSCLC, AURKB overexpression has been found to be associated with a negative prognosis, poor therapeutic response, and decreased overall survival rate, suggesting that AURKB may be a potential prognostic biomarker. In the past decades, pan-AURKs and selective AURKB inhibitors have been tested in preclinical studies, and some of them have progressed to different stages of clinical trials. Based on preclinical studies conducted on NSCLC cell lines, selective AURKB inhibitors lead cancer cells to apoptosis by causing the formation of cytokinesis defects, polyploidy and impaired chromosome alignments. Pan-AURKB inhibitors that target all AURKs for inactivation exhibit antitumor activity, and some of them tested in patients with NSCLC have shown satisfactory tolerance and a manageable safety profile. Since AURKB has different roles directly or indirectly in NSCLC progression, both pan-AURK and selective AURKB inhibitors have shown anticancer properties based on preclinical studies. Some of their Phase-I and Phase-II clinical trials have yielded desired results, encouraging future studies in this direction.