Advances in Genetic Testing Clarify Uncertain Results for Cancer Treatment

Cancer treatment is increasingly becoming personalized, with medical decisions tailored to an individual's unique genetic and molecular profile, along with their lifestyle and environmental factors. This approach, known as precision or personalized medicine, relies heavily on genetic testing to guide treatment strategies. While these tests have enhanced our ability to detect and understand cancer at the genetic level, they do not always provide definitive answers.

Genetic testing can reveal DNA variants associated with cancer, but often results include ambiguous findings called variants of uncertain significance (VUS). These are genetic changes that scientists are unable to interpret confidently as either harmful or benign. The presence of VUS can leave both patients and clinicians in a state of uncertainty, potentially complicating treatment choices.

The evolution of genomic technologies has improved our ability to identify rare and novel variants. However, understanding whether these variants affect gene function and influence cancer development or treatment response remains challenging. This uncertainty can delay clinical decisions and raises questions about the cost-effectiveness of widespread genetic testing, especially when results are inconclusive.

Enter functional genomics, a cutting-edge field that investigates how genetic variants behave within biological systems. Unlike traditional DNA reading, functional genomics examines how variants impact gene expression, protein function, cell behavior, and response to treatments. By studying cells derived from patients, researchers can determine whether a particular variant influences cancer progression or treatment resistance.

A recent study led by Stellenbosch University showcased this approach. Researchers explored a rare inherited TP53 gene variant identified through whole exome sequencing in a South African family with multiple cancer cases. Findings revealed that this variant rendered cancer cells resistant to the chemotherapy drug doxorubicin, causing cells to enter a senescent state rather than die, and also impairing immune cell function. Such insights help in understanding the clinical significance of previously uncertain genetic variants, guiding more effective personalized treatments.

Overall, advances in functional genomics stand to revolutionize cancer care by providing clearer interpretations of complex genetic data. This progress promises tailored therapies with higher success rates and renewed hope for patients navigating the uncertainties of genetic testing.