Companion Oncology – The future of individual diagnosis
Companion diagnostics are designed to measure an individual patient’s levels of proteins, genes, or specific mutations and help deliver a more specific effective therapy.
Since its inception in the late 70s, the field of Companion Diagnostics has expanded from a handful of oncology drugs with corresponding diagnostics to include multiple therapeutic areas, with oncology the largest segment.
Oncology will remain at the forefront of Companion Diagnostics and looks set for exceptional investment and growth.
The anatomy of Companion Diagnostics
Typically, Companion Diagnostics use techniques such as immunohistochemistry (IHC), in situ hybridization (ISH), nucleic acid amplification (NAAT), and gene sequencing methods such Sanger sequencing and next-generation sequencing (NGS).
A widely used, antibody-based technique that detects the presence of specific antigens or proteins in tissue. Chromogenic detection methods help visualize antibody-antigen interactions.
In Situ Hybridization
This uses denaturation of DNA or RNA to form single-stranded molecules, which naturally re-anneal to labelled probes made up of complementary nucleic acid sequences. They detect the presence or absence of specific genes or mutations.
Nucleic Acid Amplification
This involves the amplification of specific nucleic acid sequences related to a target gene or mutation, using polymerase chain reaction (PCR). PCR consists of three main steps, which are repeated many times in cycles to amplify a target DNA sequence. These three steps are:
▪ Denaturation of template DNA strands using high temperatures
▪ Annealing of oligonucleotide primers that match specific sequences in the template DNA
▪ Extension of these primers via copying of the template DNA by a DNA polymerase enzyme
This is a DNA sequencing technique that uses modified, chain-terminating dideoxynucleotides (ddNTPs). DNA fragments are first generated and terminated with a labelled nucleotide. The ddNTPs labelled with radioactive phosphorus can then be separated by gel electrophoresis and visualized via autoradiography.
Next-Generation Sequencing (NGS)
NGS is any method for DNA sequencing that’s not Sanger-based. It has largely superseded Sanger sequencing in academic or genome research and is increasingly being applied in clinical practice. NGS allows for the rapid and accurate sequencing of an entire genome at once by fragmenting DNA and sequencing those fragments in an automated, parallel manner.
There are a number of emerging trends in Companion Diagnostics.
Data and AI
Big Data and Artificial intelligence (AI) are essential in the prediction of prognosis and optimal treatment options using patient-level characteristics. As new information is added, from different sources, new patterns can be identified using AI algorithms. Look out for companies such as Foundation Medicine, Congenica, deCODe Genetics, and Illumina.
Predictive biomarkers predict response to specific therapeutic interventions, alerting physicians to the risk of specific clinical outcomes. Biomarkers are expected to play a important role in minimizing the risk of clinical trial failure.
Laboratory developed tests (LDT)
LDTs are a type of diagnostic test that is designed, performed, and used within a single laboratory. Generally much less regulated, some LDTs (such as those for ovarian and cervical cancers) have been associated with serious safety issues. Tighter regulation may be required.
Liquid biopsies are a minimally invasive way to detect mutation from circulating tumour DNA (ctDNA) found in plasma. Companies such as Roche and Amoy diagnostics sell liquid biopsies that detect epidermal growth factor receptor (EGFR) mutations (NSCLC biomarker) in ctDNA, Sysmex sells liquid biopsies that detect KRAS mutations (colorectal cancer biomarker). Illumina recently announced the launch of its first liquid biopsy solution for detecting cancer biomarkers.
In the future, liquid biopsies could be used to guide treatment, by personalizing treatment in precision medicine.
Collaboration is the key
Many large diagnostic manufacturers typically have trouble investing in diagnostic equipment, so they form partnership deals with pharmaceutical companies, who can then access the diagnostic company’s proprietary platforms.
Pharmaceutical companies tend to only develop companion tests if they believe their drug will not pass FDA scrutiny without it.
Companies to look out for:
Freenome’s multiomics blood test looks for the body's own early-warning signs for cancer. It provides a multidimensional view of the immune signatures that enable early detection.
They use their expertise in molecular biology and advanced computational techniques to recognize patterns among billions of circulating, cell-free biomarkers. They have created simple and accurate blood tests for early cancer detection that also integrate the actionable insights into health systems.
Grail’s test is called Galleri. It is a multi-cancer early detection test that can detect over 50 types of cancers, with a low false positive rate. All through a single blood sample.
Oxford Gene Technology
OGT offer over one hundred high-quality DNA FISH probes for the detection of genetic aberrations found in cancer and inherited genetic diseases. Pioneers in hybridisation technology and a leading provider of clinical research and diagnostic solutions, they work in partnership with clients to help clinical decision makers.
Vela Diagnostics offers a range of tests for the diagnosis of various infectious diseases, but also cancer. Their tests are validated for more than 20 different sample types providing a high degree of clinical versatility.
Conclusion - decreasing cost, rising accuracy
The cost of sequencing is rapidly decreasing due to increasing competition and advancing technology. Sequencing a single genome cost $100M in 2001. Illumina and Life Technologies claim to be able to sequence whole genomes for less than $1,000.
Companion Diagnostics can help select treatments, resulting in reduced costs, as expensive treatments are not wasted on patients who are unlikely to respond. It also helps patients avoid potential adverse events, reducing unnecessary hospitalizations and outpatient costs.