We all know someone with cancer. Or maybe you are currently fighting this disease or are a survivor. It is a battle against a very personal disease — a disease made up of specific genetic lesions. No longer does one have "lung cancer". For example, a patient's tumor may be driven by an EGFR indel, an ALK fusion, a KRAS point mutation, or a MET amplification. Knowing the specific genetic mutation that is driving the cancer forward is critical in the age of personalized medicine and targeted therapies.
The first step is to identify the personalized mix of genetic alterations. These genetic variants may be single nucleotide variants (SNVs), short insertions or deletions (indels), gene fusions / translocations, or gene amplifications or deletions (CNVs). Sometimes, a tumor may harbor more than one alteration. In fact, different parts of the same tumor may have different genetic make-up: an issue called tumor heterogeneity. However, the current standard of care is to use an invasive tissue biopsy to collect the cells for genotyping. A biopsy is not only limited in that it is a single point sampling spatially, it is also a single sampling of the tumor temporally — it may not represent the overall mutational landscape of the cancer.
For these reasons, we created the Resolution Bioscience’s ctDx™platform. We capture and analyzie the short, 165 DNA base fragments that are floating in a cancer patient’s blood. Using our peer-reviewed technology, we are able to analyze not only hotspot mutations, but the more complex gene fusions and copy number variations. In fact, we were the first to demonstrate the ability to detect gene fusions without prior knowledge of the breakpoint or gene partner in circulating, cell-free DNA.
When we started our company, we asked a simple question: “How can we help patients benefit from the incredible power of next generation sequencing?” That basic question drove us to develop a revolutionary platform that can:
Imagine being an oncologist treating a non-small cell lung cancer (NSCLC) patient. You know that a targeted therapy may help your patient, but which test should you order? EGFR? ALK? What about BRAF? MET amplification? What if the patient is frail or the tumor is hard to biopsy? What if you can’t wait a month for a tissue-based molecular report?
We start with 10ml of peripheral blood. We extract the circulating, cell-free DNA (cfDNA), of which a fraction of the cfDNA is from the cancer tumor (ctDNA). Through proprietary biochemistry, we molecularly tag millions of cfDNA fragments, and discover driver mutations by sequencing them on a desktop sequencer. Our cloud-based bioinformatics analyzes the data and produces a comprehensive variant report. Hotspots, indels, amplifications and fusions — we see them all in a single assay from a single sample. Our process is so efficient that we routinely multiplex samples in a single sequencing run.
After sequencing, our novel bioinformatics analyzes millions of reads. In a single assay we capture all types of mutations. The result:
In May 2015, we launched our ctDX ALK assay from our CLIA lab. We continue to validate our gene panel for NSCLC, ctDx Lung. Being a true platform, we can easily and efficiently add new genes as science discovers new driver mutations and new therapies are developed.
Our plans include developing a kit that will enable any lab with a desktop sequencer to run the Resolution ctDx platform. Sequencing data can be streamed to our cloud-based bioinformatics.
We will enable researchers around the globe to develop novel assays. We will create pan-therapy companion diagnostics (CDx) assays that can be run anywhere in the world.
Within these vials of human plasma reside the keys to understanding what is driving these patients disease. In a safe and routine blood draw, we can unlock information to help a physician direct therapy decisions.
Not every tumor can be biopsied. Not every biopsy results in enough tumor cells to give a definitive molecular profile. Biopsies can result in serious complications. Serial biopsies are not practical. As the tumor finds new ways to escape therapy, plasma offers the ability to continually monitor tumor evolution — providing critical, real-time feedback to direct therapeutic decisions.Read more