Aneuploidies characterized by abnormal changes in chromosome numbers in the cell are very well-known early events in cancer progression and are used as a diagnostic and prognostic biomarker in many malignancies. This aberration, previously considered a consequence of genomic instability, is now recognized as a potential driver of cancer development.
Dr Suruchi Aggarwal, PhD (Human Genomics), Lead, Scientific Affairs & Technical Support - Oncology, MedGenome, sheds more light on the topic and says that the continuous presence of aneuploidy state creates a selective pressure that fuels the evolution of cancer cells, dependent on the abnormal chromosome number for their survival and growth.
“Increased genomic instability, altered gene dosage, aneuploidy-induced stress response, and changes in gene expression contribute to this oncogene-like addiction. Understanding the underlying mechanisms and dependencies associated with aneuploidy is crucial for unravelling the complexities of tumour biology,” says Dr Suruchi.
Cancer treatment based on aneuploidy changes represents a promising avenue in the quest for more effective and targeted therapies against malignancies. By targeting the unique properties conferred by aneuploidy, such as increased genomic instability and altered gene dosage, researchers aim to disrupt the survival and growth of cancer cells while sparing normal cells. By targeting the mechanisms that drive chromosome missegregation and the generation of aneuploid cells, therapeutic interventions can aim to restore chromosomal stability and limit tumour evolution, says the doctor.
“Additionally, understanding the altered gene dosage resulting from aneuploidy opens up possibilities for precision medicine approaches. By selectively targeting genes that are amplified or deleted due to aneuploidy, therapies can be designed to restore the balance of gene expression and disrupt cancer cell growth,” she adds.
Furthermore, aneuploidy-induced stress responses and changes in gene expression provide additional targets for therapeutic intervention. By identifying critical signalling pathways activated in response to aneuploidy, novel drugs can be developed to selectively inhibit these pathways, leading to impaired survival and proliferation of cancer cells, according to the doctor.
This study clearly shows that by identifying and targeting the genes and their pathways in the aneuploidies in cancer cells like UCK2 gene shown, precision medicine can be achieved, says the doctor. While the development of aneuploidy-targeted therapies is still in its early stages, the potential impact on cancer treatment is promising. Dr Suruchi maintains that the “door is open for innovative treatment modalities that exploit the unique vulnerabilities associated with this characteristic aberration."