What is the role of Next-Generation Sequencing (NGS) in cancer diagnosis and treatment?

From the Guidelines

Next-generation sequencing (NGS) should be used to guide cancer diagnosis and treatment by identifying actionable mutations and predicting response to targeted therapies and immunotherapies, as recommended by the ESMO precision medicine working group in 2024 1. The role of NGS in cancer diagnosis and treatment is to enable comprehensive genomic profiling of tumors, detecting mutations, copy number variations, gene fusions, and other genomic alterations that drive cancer growth. In clinical practice, NGS is used to identify actionable mutations that can guide targeted therapy selection, such as EGFR mutations in lung cancer, BRAF V600E mutations in melanoma, or HER2 amplifications in breast cancer. Some of the key points to consider when using NGS in cancer diagnosis and treatment include:

• The ability to detect rare alterations and provide a comprehensive genomic landscape, making it superior to single-gene testing approaches
• The capacity to determine tumor mutational burden (TMB), microsatellite instability (MSI), and other biomarkers that predict response to immunotherapy with checkpoint inhibitors
• The potential to monitor for resistance mutations and disease progression through sequential testing, allowing for timely therapy adjustments
• The importance of interpreting NGS data in the context of cytogenetic data, basic disease characteristics, and other molecular issues, as highlighted in a 2019 study on the treatment of myelodysplastic syndrome 1. However, the most recent and highest quality study, published in 2024, provides the most relevant guidance on the use of NGS in cancer diagnosis and treatment, and its recommendations should be prioritized 1. Some key recommendations from this study include:
• Running tumor NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer
• Carrying out tumor NGS in clinical research centers and under specific circumstances discussed with patients
• Expanding the recommendations to encompass patients with advanced breast cancer and rare tumors such as gastrointestinal stromal tumors, sarcoma, thyroid cancer, and cancer of unknown primary.

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.