Targeting chromosomal instability and aneuploidy in cancer

Sugandha Bhatia; Kum Kum Khanna; Pascal H G Duijf

doi:10.1016/j.tips.2024.01.009

Targeting chromosomal instability and aneuploidy in cancer

Trends Pharmacol Sci. 2024 Mar;45(3):210-224. doi: 10.1016/j.tips.2024.01.009. Epub 2024 Feb 13.

Authors

Sugandha Bhatia¹, Kum Kum Khanna², Pascal H G Duijf³

Affiliations

¹ Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health and Centre for Biomedical Technologies at the Translational Research Institute, Woolloongabba, QLD 4102, Australia. Electronic address: s3.bhatia@qut.edu.au.
² QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia; Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.
³ Queensland University of Technology (QUT), School of Biomedical Sciences, Centre for Genomics and Personalised Health and Centre for Biomedical Technologies at the Translational Research Institute, Woolloongabba, QLD 4102, Australia; Centre for Cancer Biology, Clinical and Health Sciences, University of South Australia and SA Pathology, Adelaide, SA 5001, Australia; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. Electronic address: pascal.duijf@unisa.edu.au.

PMID: 38355324
DOI: 10.1016/j.tips.2024.01.009

Abstract

Cancer development and therapy resistance are driven by chromosomal instability (CIN), which causes chromosome gains and losses (i.e., aneuploidy) and structural chromosomal alterations. Technical limitations and knowledge gaps have delayed therapeutic targeting of CIN and aneuploidy in cancers. However, our toolbox for creating and studying aneuploidy in cell models has greatly expanded recently. Moreover, accumulating evidence suggests that seven conventional antimitotic chemotherapeutic drugs achieve clinical response by inducing CIN instead of mitotic arrest, although additional anticancer activities may also contribute in vivo. In this review, we discuss these recent developments. We also highlight new discoveries, which together show that 25 chromosome arm aneuploidies (CAAs) may be targetable by 36 drugs across 14 types of cancer. Collectively, these advances offer many new opportunities to improve cancer treatment.

Keywords: CRISPR; aneuploidy; cancer; chromosomal instability; genomic instability; oncology.

Publication types

Review

MeSH terms

Aneuploidy*
Chromosomal Instability
Humans
Neoplasms* / drug therapy
Neoplasms* / genetics