[Column] Why – and when – do we conduct genomic testing for cancer patients?

Various genetic mutations cause cancer, and even the same cancer can have different genetic characteristics in different patients.

In cancer treatment, “precision medicine” refers to examining which genetic mutations are present in each patient's tumor and selecting the drug expected to have the greatest effect on each patient based on this information.

It is currently one of the most essential paradigms in oncology. Genomic testing, specifically Next-Generation Sequencing (NGS), plays a key role in this area. NGS analyzes tens of millions of DNA fragments simultaneously to decipher genetic information quickly and precisely. This allows us to find genetic mutations hidden in cells and identify each patient's genetic characteristics.

Humans are known to have about 20,000 genes, and whole-genome sequencing is a test that analyzes all of them.

While this test is very informative and can provide information on a wide range of genetic variants, it has the disadvantage of being data-heavy and time-consuming to analyze. Therefore, most hospitals use targeted sequencing, which involves sequencing hundreds of clinically important genes in a panel and analyzing only those genes.

NGS testing can be performed using various specimens, depending on the purpose.

Most commonly, tumor tissue is used for testing. This method often detects tumor-specific mutations because the genes are extracted and analyzed directly from the tumor cells. However, sometimes, the tumor is too deep to be tested, or the risk involved in performing a biopsy is too high.

Recent advances in technology have allowed NGS testing to be performed using a liquid biopsy, a technique that detects circulating tumor DNA in a patient's blood sample. This is significantly more reliable than testing with tissue samples.

NGS testing has multiple purposes in cancer therapy, also predicts resistance to targeted therapies

NGS testing is used clinically in cancer patients for several purposes. First, it provides the information needed to select a specific cancer treatment. Second, it can identify some genetic variants that are responsive or resistant to certain drugs.

For example, targeted therapies have been developed for different genetic variants in lung cancer. Whereas previous tests for each genetic variant were performed separately, NGS testing can identify these variants in a single test, predicting which drug will be most effective for each patient and guiding treatment.

Sometimes, the presence or absence of a particular genetic variant predicts resistance to a targeted therapy. This information is also crucial when choosing a treatment agent, so NGS testing can be helpful in various situations.

The second is to identify potential candidates for clinical trials. If an NGS test reveals a gene mutation that is targeted by a drug, you may be offered the opportunity to participate in a clinical trial of a new drug that targets the mutation.

Recently, the Korean Society of Medical Oncology conducted a clinical trial (KOSMOS-II study, https://ksmo.or.kr/Pages/KPMNG/kpmng02.aspx) in Korea to provide personalized drug therapy based on genomic variants. If mutations can be targeted by targeted therapies through NGS testing, these clinical trials may lead to new treatment opportunities.

The third is for accurate diagnosis. Based on advances in molecular genetics, some cancers can be classified based on the genetic alterations in tumor cells. In recent years, the pathologic diagnosis of a tumor has been determined by the presence or absence of genetic alterations, so NGS testing can improve diagnostic accuracy, distinguish between cancers with similar morphologies but different molecular characteristics, and enable more appropriate treatment.

The fourth is when a hereditary cancer is suspected. Certain cancers have a genetic mutation that increases the risk of developing them in families. For example, the BRCA1 and BRCA2 gene mutations associated with breast and ovarian cancer can run in families, and the presence of these mutations significantly increases the risk of developing cancer.

Identifying these genetic variants through NGS testing can alert family members with the variants to the possibility of cancer and help them plan early screening or preventive treatment.

NGS testing, mainly for patients with metastatic-stage solid cancers,  also recommended for hereditary cancers

Not all cancer patients undergo NGS testing. It is typically reserved for patients with metastatic-stage solid tumors. It is recommended even for early-stage cancers if certain high-risk mutations are expected if it is performed to confirm an accurate diagnosis or if hereditary cancer is suspected.

NGS testing has become a very important tool in the rapidly evolving field of oncology. It allows us to provide personalized treatment tailored to a patient's genetic characteristics, predict prognosis, and explore new treatment possibilities through clinical trials. I hope this article will help patients and their caregivers understand the implications of NGS testing and work with their healthcare team to develop an optimal treatment plan.