In recent years, Next-Generation Sequencing (NGS) has revolutionized the field of oncology, fundamentally transforming cancer diagnosis, monitoring, and treatment. As an oncologist, I witness the profound impact of NGS in daily practice, where it provides critical insights into tumor biology and facilitates the customization of treatment based on each patient’s unique genetic profile. This capability to examine tumors at the molecular level represents a significant paradigm shift toward precision medicine, enabling us to move beyond conventional, one-size-fits-all approaches to personalized treatment strategies aimed at achieving optimal outcomes for individual patients.
Liquid Biopsies
One of the most promising applications of NGS in oncology is the development of liquid biopsies. By analyzing circulating tumor DNA (ctDNA) in a patient’s blood, liquid biopsies offer a minimally invasive approach for detecting cancer-associated mutations and monitoring tumor dynamics over time. This technology is particularly valuable for tracking minimal residual disease (MRD)—small remnants of cancer that persist after treatment—and serves as a reliable predictor of recurrence risk. NGS based liquid biopsies enable the detection of emerging genetic mutations and resistance markers, often before clinical signs of relapse become evident. The potential for early intervention provided by this approach is invaluable, allowing us to adjust treatments in real time to improve patient outcomes.
Comprehensive Genomic Profiling
Traditional single-gene testing has evolved into more comprehensive methodologies. Today, we increasingly employ NGS panels capable of analyzing hundreds of genes simultaneously—a strategy known as Comprehensive Genomic Profiling (CGP). CGP enables the identification of a wide spectrum of genetic alterations, including mutations, gene fusions, and copy number variations, all of which can influence tumor biology and therapeutic responses. For instance, in lung cancer, CGP facilitates the detection of rare mutations such as ALK and ROS1, which are amenable to targeted therapies. Similarly, in breast cancer, CGP identifies actionable markers, including BRCA mutations, guiding personalized treatment decisions. By ensuring that even uncommon genetic drivers are recognized, CGP maximizes the potential for every patient to benefit from the most appropriate and effective treatment options.
Predictive Biomarkers for Immunotherapy
Immunotherapy has emerged as a cornerstone of cancer treatment, yet its effectiveness varies significantly among patients. NGS plays a pivotal role in identifying predictive biomarkers, such as tumor mutational burden (TMB) and microsatellite instability (MSI), which help determine a patient’s likelihood of responding to immunotherapy. For instance, tumors with high TMB are more responsive to immune checkpoint inhibitors. The ability to detect these biomarkers enables clinicians to make evidence-based decisions about immunotherapy, optimizing treatment selection while sparing patients from unnecessary side effects and financial burdens when their tumors are unlikely to benefit from this approach.
Real-Time Monitoring and Adaptive Treatment
One of the most transformative advances enabled by NGS is the ability to monitor tumor evolution over time. By sequencing (ctDNA) at multiple stages during treatment, we can detect emerging resistance mutations and adjust therapies before clinical disease progression occurs. This dynamic, real-time monitoring strategy— often referred to as “adaptive treatment”—ensures that patients receive therapies tailored to the evolving genetic landscape of their tumors, maximizing treatment efficacy and improving overall outcomes.
AI and Data Integration in Oncology
NGS generates vast amounts of complex data, making artificial intelligence (AI) increasingly indispensable for effective interpretation. Machine learning algorithms are pivotal in uncovering patterns within genetic data that inform treatment decisions and predict outcomes. Looking ahead, the integration of AI, NGS, and clinical data will further refine precision oncology, enabling oncologists to deliver more personalized and accurate care.
NGS is more than a diagnostic tool—it is a gateway to understanding cancer at its molecular core. It equips oncologists with a powerful arsenal to detect, target, and monitor tumors in ways previously unimaginable. As technological advances continue to reshape the landscape of cancer care, NGS will remain at the forefront, driving innovations that make treatments more effective, less toxic, and highly individualized. For those of us on the front lines, NGS heralds a future of unprecedented hope and transformative possibilities in the fight against cancer.
Dr. Mahendra Perera Consultant in Clinical Oncology & Radiotherapy/ Senior Lecturer Oncology at Dr. Neville Fernando (State) Teaching Hospital, Malabe, Srilanka