Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer

Alessio Stefani; Geny Piro; Francesco Schietroma; Alessandro Strusi; Emanuele Vita; Simone Fiorani; Diletta Barone; Federico Monaca; Ileana Sparagna; Giustina Valente; Miriam Grazia Ferrara; Ettore D'Argento; Mariantonietta Di Salvatore; Carmine Carbone; Giampaolo Tortora; Emilio Bria

doi:10.3389/fonc.2022.1026020

Unweaving the mitotic spindle: A focus on Aurora kinase inhibitors in lung cancer

Front Oncol. 2022 Oct 27:12:1026020. doi: 10.3389/fonc.2022.1026020. eCollection 2022.

Authors

Alessio Stefani^{1

2}, Geny Piro^{1

2}, Francesco Schietroma^{1

2}, Alessandro Strusi^{1

2}, Emanuele Vita^{1

2}, Simone Fiorani^{1

2}, Diletta Barone^{1

2}, Federico Monaca^{1

2}, Ileana Sparagna^{1

2}, Giustina Valente^{1

2}, Miriam Grazia Ferrara^{1

2}, Ettore D'Argento^{1

2}, Mariantonietta Di Salvatore^{1

2}, Carmine Carbone^{1

2}, Giampaolo Tortora^{1

2}, Emilio Bria^{1

2}

Affiliations

¹ Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy.
² Section of Medical Oncology, Università Cattolica del Sacro Cuore, Rome, Italy.

Abstract

Lung cancer is one of the most aggressive malignancies, classified into two major histological subtypes: non-small cell lung cancer (NSCLC), that accounts for about 85% of new diagnosis, and small cell lung cancer (SCLC), the other 15%. In the case of NSCLC, comprehensive genome sequencing has allowed the identification of an increasing number of actionable targets, which have become the cornerstone of treatment in the advanced setting. On the other hand, the concept of oncogene-addiction is lacking in SCLC, and the only innovation of the last 30 years has been the introduction of immune checkpoint inhibitors in extensive stage disease. Dysregulation of cell cycle is a fundamental step in carcinogenesis, and Aurora kinases (AURKs) are a family of serine/threonine kinases that play a crucial role in the correct advance through the steps of the cycle. Hyperexpression of Aurora kinases is a common protumorigenic pathway in many cancer types, including NSCLC and SCLC; in addition, different mechanisms of resistance to anticancer drugs rely on AURK expression. Hence, small molecule inhibitors of AURKs have been developed in recent years and tested in several malignancies, with different results. The aim of this review is to analyze the current evidences of AURK inhibition in lung cancer, starting from preclinical rationale to finish with clinical trials available up to now.

Keywords: AURK inhibitors; Aurora kinase (AURK); cancer; lung; mitosis; oncology.

Publication types

Review