Innovation in drug discovery and development has led to a dramatic change in the way we think about cancer. Healthcare is rapidly moving toward more personalized care, a shift solidified in this year's State of the Union address as President Barack Obama announced a new $215-million precision medicine initiative. The President went on to call it one of the biggest opportunities for breakthrough medicine that society has ever seen.
While precision oncology means different things to different people, at its core it involves testing an individual's tumor to identify mutations that are used to match that patient to the right therapy. While whole genome and exome sequencing are valuable approaches for researching changes in the broader genome, targeted next-generation sequencing (NGS) is leading the way in providing a cost-effective and scalable approach to detect oncology driver mutations in solid tumor samples. Furthermore, targeted sequencing eliminates the expensive and time-consuming process used today of sequentially testing each individual variant.
Next-Generation Sequencing as a Companion Diagnostic
Supporting this approach, pharmaceutical companies are forming partnerships with leading genetic technology providers to develop companion diagnostics in conjunction with new targeted oncology therapies to advance the future of cancer care. However, there are number of challenges associated with creating a new and unique test for each new oncology drug. Taking a more unified approach, Thermo Fisher Scientific is working closely with leading pharmaceutical companies to develop a universal NGS oncology test that would enable the simultaneous analysis of multiple solid tumor genes to inform multiple targeted therapies.
This multi-biomarker, NGS-based approach helps accelerate the development of these promising therapies, and ultimately can help physicians identify clinical trials that may provide their patients with the best possibility of a successful outcome. Additionally, multi-biomarker tests that simultaneously analyze many genes can eliminate the need to develop a unique companion diagnostic test for each new therapy.
A Paradigm Shift for Clinical Trials
In pursuit of a similar goal, the National Cancer Institute (NCI) and ECOG-ACRIN announced a first-of-its-kind oncology clinical trial at the American Society of Clinical Oncology (ASCO) conference in June. The NCI Molecular Analysis for Therapy Choice (MATCH) program aims to sequence the tumors of 3,000 patients across the United States using Thermo Fisher's Ion Torrent NGS system and Oncomine reagents. Targeted tumor sequencing will be conducted at four centralized laboratories - the NCI Molecular Characterization Laboratory in Frederick, Maryland, the University of Texas MD Anderson Cancer Center in Houston, Boston's Massachusetts General Hospital and Yale University – ultimately to enroll 1,000 qualifying patients.
The trial marks a paradigm shift for clinical trials. Using the sequencing results, the study's lead investigators will assign eligible program participants to one of up to 20 trial arms based on the genetic alterations associated with their tumor, rather than their type of cancer. The trial will include about 20 or more different study drugs from multiple pharmaceutical partner companies. Multi-arm study designs like NCI-MATCH allow researchers to cast a wider net, which helps take into account relatively rare tumor mutations and helps drive the development of promising new therapies.
Because targeted NGS technology enables simultaneous sequencing of a wide range of genetic alterations, including single nucleotide variants (SNV), small insertions and deletions (indels), copy number changes and chromosomal translocation, researchers can efficiently screen the tumor biopsies for hundreds of known cancer-causing mutations. When used in conjunction with Ion AmpliSeq technology's low DNA and RNA sample input requirements from FFPE tissue, accurate and reliable sequence analysis can also be obtained across a large range of tumor sample types, including small biopsies and fine needle aspirates.
ECOG-ACRIN Laboratory Lead and Head of Pathology and Laboratory Medicine at MD Anderson, Stanley R. Hamilton, M.D., recently stated: “Clinical trials of this size and type must rely on technology that can accurately detect a wide range of infrequent gene alterations with a single assay using small amounts of DNA and cDNA from a formalin-fixed paraffin-embedded biopsy specimen or fine needle aspiration specimen. These same assay requirements will often apply to enabling precision medicine.”
Precision medicine has the potential to revolutionize the healthcare system by leading a new approach to treat cancer patients. Driving this era of targeted therapies and more efficient clinical trials will be the ever-expanding knowledge of genetic and clinical research data facilitated through advanced targeted sequencing technology. It is the application of these innovative tools that will play a key role in helping health care providers and their patients wage a stronger fight against cancer.
Mike Nolan is the vice president and general manager of Oncology at Thermo Fisher Scientific Inc. The company, a world leader in serving science, supports customers with life sciences research, analytical challenges, patient diagnostics and laboratory productivity. Its brands include Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific and Unity Lab Services.