NGS platforms can sequence millions of small fragments of DNA. The genome sequences multiple times to provide accurate data and insight for variations. It can be modified to cater to different sizes of genomes and areas of interest. On the other hand, precision medicine involves designing a treatment based on a person's pathogenic molecular alterations. It can identify genetic differences, brought by varying patient backgrounds, including deleterious mutations and varying levels of expression in drug targets and metabolizing proteins. Identification of molecular aberrations and then linking to treatment became much easier due to the accuracy, increasing efficiency, and affordability of next-generation sequencing (NGS). It is widely used by oncologists to sequence patient's tumors to pinpoint alterations and then formulate a treatment scheme targeting molecular aberrations which fuel tumor metastasis.
Drug-related fatalities can be prevented by practicing personalized medicine. Early detection of disorders through disease panels and identification markers in pharmacogenetics through amplicon sequencing to customize treatments became reachable through NGS. Patient outcomes became more desirable when sequencing results were used to match patients to a treatment based on their cancer's genome (Inserro, 2020). In one study, when advanced cancer patients were given a treatment matched to their cancer's genome, overall response rate (27% vs. 5%), time to treatment failure (5.2 vs. 2.2 months), and survival (13.4 vs. 9 months) were improved compared to patients without sequencing-matched therapy. Progression-free survival, or the time between the start of treatment and the growth of cancer, of patients with treatments matched to their tumor mutations, was higher than that of patients receiving non-matched therapy (86 vs. 49 days). Many studies indicate that using sequencing results to inform patient treatment schemes shows clinical benefit and improved survivability. A well-developed personalized drug treatment and genome analysis can save resources and improve patient treatment.
For one instance, a 24-year-old male cancer patient was unsuccessfully treated for a chemoresistant and invasive tumor in the neck and throat for 20 years. Researchers created a new cell line from his excised tumor by sequencing the tumor DNA through NGS. From the results, they were able to detect human papillomavirus (HPV) gene expression causing tumor growth. Before trying precision medicine, repeated surgery was the only option to slow down tumor progress and metastasis. Based on the sequencing results, the researchers were able to identify a better therapeutic solution featuring three anticancer drugs on the reprogrammed patient-derived cells: vorinostat, cidofovir, and dihydroartemisinin which are historically used against HPV-positive cell lines. Only vorinostat demonstrated a threefold selectivity for cancer cells compared with healthy cells. Treatment of the patient with vorinostat, an inexpensive previously overlooked anticancer drug, produced positive results with succeeding tumor shrinkage and stabilized tumor size.
The incorporation of NGS to cancer treatments is still in its primary stages as there are no randomized controlled trials supporting an NGS-based treatment approach. The difficulty to obtain a sufficiently large population to support a randomized controlled trial for each cancer sub-type NGS can identify remains a huge hurdle to overcome. Varying reports on the efficacy of NGS-mediated cancer treatment reflects the complexity of treating advanced cancer patients whose tumors may have different mutations within cells and/ or may have different cells within the same tumor which makes them highly heterogeneous.
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