Decoding cancer at the molecular level: The transformative role of next-generation sequencing in oncology

Matias Melendez

doi:10.35841/ aamor-9.3.298

Commentary - Journal of Molecular Oncology Research (2025) Volume 9, Issue 3

Decoding cancer at the molecular level: The transformative role of next-generation sequencing in oncology

Matias Melendez ^*

Department of Molecular Oncology, Barretos Cancer Hospital, Brazil

*Corresponding Author:: Matias Melendez
Department of Molecular Oncology, Barretos Cancer Hospital, Brazil
E-mail: melendez.matias@barretosoncology.br

Received: 01-Aug-2025, Manuscript No. AAMOR -25-166745; Editor assigned: 02-Aug-2025, PreQC No. AAMOR -25-166745(PQ); Reviewed: 18-Aug-2025, QC No. AAMOR -25-166745; Revised: 22-Aug-2025, Manuscript No. AAMOR -25-166745(R); Published: 29-Aug-2025, DOI: 10.35841/ aamor-9.3.292

Citation: : Melendez M. Decoding cancer at the molecular level: The transformative role of next-generation sequencing in oncology. J Mol Oncol Res. 2025;9(3):292.

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Introduction

Cancer is a genetically complex and heterogeneous disease that requires equally complex approaches for its diagnosis and treatment. One of the most transformative tools in molecular oncology research today is Next-Generation Sequencing (NGS) — a powerful technology that allows for the high-throughput analysis of DNA and RNA sequences. NGS has revolutionized the way researchers and clinicians understand cancer biology, paving the way for precise diagnostics, individualized treatment strategies, and real-time monitoring of tumor evolution. In contrast to traditional sequencing techniques, NGS provides an unprecedented depth and speed of genomic information. Its ability to simultaneously analyze multiple genes or entire genomes has positioned it as an indispensable tool in cancer genomics. As oncology shifts toward precision medicine, NGS is emerging as the cornerstone of personalized cancer care [1, 2].

The future of NGS is poised for further breakthroughs. Emerging platforms such as single-cell sequencing, long-read sequencing, and multi-omics integration promise deeper insights into tumor biology. AI-driven analytics are improving variant interpretation and clinical decision support, while cost reductions and automation are expanding access to this technology. NGS technology allows comprehensive profiling of cancer genomes, exomes, and transcriptomes, offering insights into genetic mutations, copy number variations, gene fusions, and other molecular alterations that drive tumor development. This detailed mapping is essential for identifying actionable mutations and selecting targeted therapies tailored to individual patients. For example, in non-small cell lung cancer (NSCLC), NGS panels can detect mutations in EGFR, ALK, KRAS, and other key oncogenes. These findings guide the use of targeted inhibitors, improving treatment efficacy and patient survival. Similarly, in breast cancer, NGS aids in detecting BRCA1/2 mutations, informing risk assessment and preventive strategies such as prophylactic surgery or PARP inhibitor therapy [3, 4].

One of the most promising applications of NGS is in liquid biopsy, which involves analyzing circulating tumor DNA (ctDNA) from blood samples. This non-invasive method offers several advantages over tissue biopsies — including real-time monitoring, reduced procedural risks, and the ability to capture tumor heterogeneity. NGS-powered liquid biopsies are now being used to detect minimal residual disease, monitor therapeutic response, and identify resistance mutations. For instance, the emergence of the T790M mutation in EGFR-positive NSCLC patients undergoing tyrosine kinase inhibitor therapy can be rapidly identified using ctDNA sequencing, allowing timely adjustments to treatment plans [5, 6].

Pharmaceutical companies are increasingly using NGS data to develop and stratify clinical trials. By categorizing patients based on their genomic profiles, trials can focus on specific molecular subtypes, thereby increasing the success rate and relevance of new treatments. NGS is also critical for discovering novel drug targets and resistance mechanisms. For example, sequencing recurrent tumors has revealed mutations in PIK3CA, TP53, and PTEN, guiding the development of second-line therapies. Furthermore, NGS contributes to basket trials, where patients with different cancer types but shared mutations receive the same targeted therapy — a concept that is rapidly gaining traction [7, 8].

Despite its many benefits, integrating NGS into clinical practice poses several challenges. The interpretation of massive sequencing data requires advanced bioinformatics infrastructure and skilled personnel. Additionally, the clinical significance of many detected variants — particularly variants of unknown significance (VUS) — remains unclear, complicating decision-making. Cost and accessibility also limit widespread adoption, especially in low-resource settings. Moreover, ethical and regulatory considerations related to genetic data privacy and incidental findings necessitate robust policies to protect patient rights [9, 10].

Conclusion

Next-Generation Sequencing has emerged as a transformative force in molecular oncology research, offering a deeper understanding of cancer at the genomic level. From diagnostics to drug development, and from monitoring treatment response to predicting recurrence, NGS is reshaping every aspect of oncology. The continued evolution of NGS will likely result in real-time, bedside genomic diagnostics and adaptive treatment strategies that evolve alongside the tumor. Such advancements bring us closer to the ideal of truly personalized oncology — where treatment is as dynamic and unique as each patient’s cancer. While challenges remain, the integration of NGS into standard cancer care holds immense potential for improving outcomes, reducing treatment toxicity, and enabling precision medicine on a global scale. With continued innovation and ethical oversight, NGS is set to remain a pillar of modern oncology for years to come.