PhD Defense: Clinical implementation of new diagnostic modalities in the era of precision oncology; Path to Precision

The field of oncology in the Netherlands is facing a significant challenge. Over the years, researchers have come to understand that cancer is primarily a disease of DNA. Mutations in DNA lead to uncontrolled cell growth, resulting in the formation of cancer cells. While some mutations are inherited, most occur throughout life due to factors like UV exposure or smoking.

As this understanding grew, so did the importance of DNA research, initially for scientific purposes to better comprehend cancer. However, it soon became apparent that DNA research could also benefit cancer patients directly. Genes like BRCA1 and BRCA2 were identified as linked to familial breast cancer, enabling personalized treatment based on DNA analysis. Moreover, mutations offer a promising avenue for targeted cancer therapy. By identifying specific genetic signals driving cancer growth, treatments can be tailored to target these signals directly. This personalized approach to treatment, often termed precision medicine, is revolutionizing cancer care.
While DNA research has slowly integrated into clinical practice over the years, its development has accelerated significantly in the past decade. This progress has led to an explosion of treatment possibilities, with many new drugs expected to enter the market in the coming years.

Despite these advancements, the current healthcare system is ill-prepared to handle the influx of DNA testing expected in the coming years. The piecemeal expansion of DNA testing across different laboratories has resulted in a fragmented diagnostic system. Streamlining this process is essential for meeting the growing demand for DNA testing in cancer diagnostics. One potential solution is whole-genome sequencing (WGS), a comprehensive DNA test that examines a patient's entire genome. WGS offers a forward-looking approach to diagnostics, ensuring every patient receives a thorough DNA analysis, regardless of tumor type.
The feasibility and clinical validity of WGS were demonstrated in the 'WIDE' study. Furthermore, WGS identified treatment options for 71% of patients with metastatic cancer. Additionally, WGS detected previously unknown hereditary mutations, highlighting its diagnostic utility. Further studies focused on the diagnostic value of extensive DNA testing, particularly in complex cancers like sarcomas and cases where the primary tumor is unknown. These studies underscored the potential of DNA analysis to guide treatment decisions and potentially improve patient outcomes.

Despite these advancements, challenges remain, particularly regarding the integration of genetic counseling into routine clinical practice. Strategies are being explored to efficiently incorporate genetic counseling into the diagnostic process while ensuring all relevant hereditary conditions are detected.
The discussion around DNA-based precision oncology also extends to cost-effectiveness. While DNA testing offers numerous benefits, its upfront costs and uncertain long-term savings pose challenges for widespread adoption. However, as the cost of DNA sequencing continues to decline, its broader implementation becomes increasingly feasible. Ultimately, realizing the full potential of DNA-based precision oncology requires a concerted effort to overcome logistical, financial, and ethical challenges. By embracing emerging technologies and fostering collaboration across healthcare sectors, the Netherlands can establish a forward-thinking diagnostic system that maximizes the benefits of precision oncology for all cancer patients.