We, as a society, are standing on a precipice. “Precision medicine” and “personalized care” used to be jargony buzzwords that, while exciting, meant little to anyone outside the healthcare community. But by unlocking the potential of next-generation sequencing, we can take a leap forward in making this a reality.
The completion of the Human Genome Project at the beginning of the 21st century successfully mapped all human genes and paved the way for a rapid, affordable and accurate method of genome analysis known as next-generation sequencing or NGS. NGS builds on the original DNA sequencing technology, dramatically increasing speed and accuracy while reducing manpower and cost. This allows sequencing to be used in many practical applications.
Within the healthcare community, NGS has the potential to be a powerful prognostic and diagnostic tool. The technology provides highly specific information from large areas of an individual’s DNA, often before clinical signs and symptoms of a disease appear. As such, physicians can diagnose and better predict the future development of the disease, as well as a patient’s response to certain drugs.
In the past, painting a picture of an individual’s disease has required input from multiple different sources, such as numerous different pathology tests and a patient’s response (or lack of) to treatments over the course of the disease. However, the broad scope of information provided by NGS at the beginning of a patient’s journey leads to a paradigm change, enabling precision medicine. For example, physicians can now select and estimate individual probabilities for treatment options rather than selecting treatment empirically and adjusting based on its effect.
The diagnosis and treatment of patients with cancer is one area that could potentially benefit radically from the insights offered by NGS. Indeed, this may ultimately prove to be the most critical advance in healthcare since the breakthrough of antibiotics. Prior to the discovery of bacteria, and the ultimate development of antibiotics for the treatment of bacterial infection, the lack of specific treatments meant an infection was often lethal. Today, specific and effective treatment options for different types of bacteria are available. Hopefully, we’ll soon have the same level of understanding and a growing variety of specific treatment options when it comes to different types of tumors.
A gold mine of data for drug discovery
The in-depth genetic coverage made possible by NGS provides immense sets of valuable patient information that can be mined to identify new patterns and understanding of diseases. Data mining plays a growing and essential role in the identification of new targets for drug discovery. Analyzing large sets of NGS patient data offers insight into both singular genetic mutations common in specific types of tumors and quantitative scores like tumor mutational burden for the prediction of immune therapy response.
Professional organizations, academia, individual providers and other industry professionals are recognizing the potential of NGS in drug discovery. For instance, the American Society for Clinical Oncology (ASCO) CancerLinQ initiative collects data and leverages analytics to empower the oncology community to improve the treatment and quality of life of cancer patients. CancerLinQ integrates clinical data with diagnostic laboratory data, allowing for real-world analysis and quality improvement. By making this type of information accessible, the pharmaceutical industry can efficiently look at patient populations, identify genetic targets and investigate new drugs more quickly than ever before—ultimately allowing more drugs to come to market at a more rapid pace.
Identifying patients’ markers for optimal long-term treatment
The number of new cancer therapies being approved or in the late-stage trial is skyrocketing. But with all these options and countless combinations to choose from, how will doctors decide which is best for their patients?
Identifying patients’ genetic makeup early on is critical to getting the benefits of these personalized therapies. Sequencing allows doctors to look at a patient holistically and better understand potential tools to treat that person’s particular disease—whether it be immunotherapy, targeted treatment, chemotherapy or a combination of these. NGS is one of the best means for determining which of these many options will work to treat a specific patient and his or her tumor.
For example, NGS allows doctors to assess tumor mutational burden (TMB) to identify those people most likely to recognize a clinical benefit from immunotherapy. TMB was a major topic at this year’s oncology meetings, including the American Association of Cancer Research and ASCO, and is currently one of the most exciting areas of cancer research. TMB counts the number of mutations across a selected set of genes and can determine how likely it is for immunotherapy to be efficacious for a particular patient. Only NGS provides the required broad scope of information promptly for physicians to make this decision so that the appropriate patients can get the full benefit of immunotherapy.
Currently, the use of NGS is only common in large centers of excellence like MD Anderson and Memorial Sloan Kettering. Smaller treatment centers, when they do evaluate a patient’s genes, test for specific ones—like EGFR or KRAS—in the hopes of identifying a particular targeted therapy that may be effective. This is because NGS platforms consist of multiple instruments which, in most systems, are not well integrated, leading to complex processes that require a level of expertise and time not feasible for a lab that isn’t solely dedicated to sequencing. A high degree of automation combined with software support for the clinical interpretation of the results is key for high ease of use from testing a sample to the result report. Luckily there are newer, integrated NGS systems, like QIAGEN’s GeneReader, that include bioinformatics software for analysis and result in interpretation support, allowing the technology to be used by smaller labs.
A behind-the-scenes view
Over a century ago, the X-ray was discovered, a scientific breakthrough that allowed physicians to see their patients’ bones. Almost 50 years ago, computerized tomography scans allowed for detailed body scans of not only bone but blood vessels and soft tissue. Now, NGS is offering a new, even closer look at the body—a unique view of an individual’s DNA, the very building blocks of human life and the foundation of biochemical processes.
Ultimately, genetic sequencing will be as common as getting an X-ray at the hospital—this is already true in areas like prenatal care, where expectant mothers can routinely test for fetal gender and inherited disorders like trisomy 13, 18, 21 and beyond. By large-scale adoption of NGS in the oncology space using platforms that allow even small labs to accurately and efficiently generate and interpret NGS data, almost every part of today’s cancer paradigm—discovery and development of therapeutics, diagnosis and treatment of patients—will be forever altered. With the press of a button, NGS can bring meaningful information to all members of the oncology community.
Dr. Volker Liebenberg is senior director of MDx Medical and Scientific Affairs at QIAGEN.