From the Guidelines
Next-generation sequencing (NGS) is a crucial tool in cancer diagnosis and treatment, enabling comprehensive genomic profiling of tumors and identifying actionable mutations that can be targeted with specific therapies, as recommended by the ESMO precision medicine working group in 2024 1.
Role of NGS in Cancer Diagnosis
NGS technologies allow clinicians to identify specific genetic mutations, copy number variations, gene fusions, and other genomic alterations that drive cancer growth. In cancer diagnosis, NGS helps classify tumors more precisely than traditional histopathology alone, distinguishing between subtypes that may appear similar under a microscope but have different genetic profiles requiring distinct treatment approaches.
NGS in Treatment Selection
For treatment selection, NGS identifies actionable mutations that can be targeted with specific therapies, such as:
- EGFR mutations in lung cancer (treated with osimertinib or erlotinib)
- BRAF V600E mutations in melanoma (treated with dabrafenib/trametinib)
- HER2 amplifications in breast cancer (treated with trastuzumab) NGS also enables liquid biopsy testing, where circulating tumor DNA from blood samples can be analyzed to monitor treatment response, detect minimal residual disease, or identify resistance mutations without invasive tissue biopsies.
Additional Benefits of NGS
Additionally, NGS helps determine tumor mutational burden and microsatellite instability status, which predict response to immunotherapy agents like pembrolizumab or nivolumab. The technology also supports pharmacogenomic profiling to predict drug metabolism and toxicity risks. As costs decrease and turnaround times improve, NGS is increasingly becoming standard of care in oncology, allowing for truly personalized cancer treatment based on each patient's unique tumor genomic profile, as discussed in the context of non-small cell lung cancer 1 and other types of cancer 1.
Clinical Recommendations
The ESMO precision medicine working group recommends running tumor NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer, as well as in clinical research centers and under specific circumstances discussed with patients 1. In the context of myelodysplastic syndrome, NGS can be used for diagnosis, classification, prognostication, disease surveillance, and identification of patients suitable for targeted treatment, although prospective clinical studies are needed to understand how to interpret NGS data 1.
From the Research
Role of Next-Generation Sequencing in Cancer Diagnosis
- Next-generation sequencing (NGS) has dramatically increased sequencing data output and transformed biomedical investigations, enabling the generation of genetic data specific to patients from tumor tissue samples 2.
- NGS allows for the detection of novel diagnostic and rare cancer mutations, translocations, inversions, insertions, and deletions, as well as the detection of copy number variants and familial cancer mutation carriers 3.
- The technology has many advantages, including the ability to fully sequence all types of mutations for a large number of genes, sensitivity, speed, and relatively low cost compared to other sequencing modalities 3.
Role of Next-Generation Sequencing in Cancer Treatment
- NGS enables targeted therapies by providing genetic data specific to patients, allowing for the prioritization of effective therapies based on the tumor-specific genotype 2.
- The field of precision cancer therapy is continuously growing, and NGS has improved the management and treatment of numerous cancers by providing less toxic and more efficient therapies compared to conventional chemotherapies 2.
- NGS can be used to identify new and rare mutations in cancer genes, detect inherited cancer mutations, and search for specific mutations in circulating tumor DNA in blood plasma and other body fluids 4.
Personalized Medicine and Next-Generation Sequencing
- Combining NGS with the CRISPR/Cas9 system has the potential to speed up the identification, validation, and targeting of high-value targets, enabling personalized or precision medicine 5.
- NGS and CRISPR/Cas9 can help improve cancer treatment choices by allowing for the direct targeting of tumor genes in cancer cells, eliminating genetic changes that lead to tumor growth and metastatic capability 5.
- NGS is widely used to realize principles of precision therapy in the management of cancer patients, with guidelines defining its routine use in patients with advanced cancers such as non-squamous non-small cell lung cancer, prostate cancer, ovarian cancer, and cholangiocarcinoma 4.