The Laboratory for Advanced Medicine (LAM), a biotechnology company headquartered in the US, offers non-invasive, early stage cancer detection tests that will use the IvyGene Platform. These IvyGene tests are based on detecting genomic DNA shed by cancer cells into the blood stream. By assessing cell-free DNA found in blood samples, the company can measure the extent to which methyl groups are present in DNA at certain locations in order to detect the presence of cancer. Many cancers demonstrate very distinctive DNA methylation patterns, making this an effective way to detect a very small number of cancer cells in the body.
LAM employs artificial intelligence and machine learning approaches to identify cancer-specific DNA methylation markers. The company has amassed a huge biobank of patient blood samples, which has allowed it to develop a series of such diagnostic tests. Unlike traditional genetic tests, which identify inherited mutations and provide information on someone’s likelihood of developing a particular cancer, the IvyGene tests will provide a real-time indication of whether cancer is present or not at the time of testing and allow physicians to monitor the overall tumor response of patients who are undergoing treatment.
The IvyGene test that is currently available measures DNA methylation at sites that have been shown to be extensively methylated in liver, breast, lung and colon cancers. The company believes that by measuring DNA methylation at certain sites in DNA shed into the circulation, these cancers can be detected as early as stage I. Patients can request the test through their physician, who will draw and ship their blood samples to a laboratory for analysis. The patient’s physician will then receive the results within five business days.
See a video below on how the test works:
Medgadget had the opportunity to ask Dr. Richard Van Etten, Chief Medical Officer of the Laboratory for Advanced Medicine, some questions about the test.
Conn Hastings, Medgadget: Please give us an overview of current cancer diagnostic technologies and the importance of early detection.
Dr. Richard Van Etten, The Laboratory for Advanced Medicine: Cancer diagnostic and screening procedures can be broken down into three main categories: Direct visualization procedures, imaging techniques and in vitro diagnostic tests. Despite several technical advances in many areas of cancer diagnostics, the detection and imaging of human cancer remain poor. The progression of cancer to late stages without the appearance of symptoms is one of the main reasons that cancer is one of the leading causes of death. Therefore, the early detection of cancer, before a person shows any signs of illness, would increase the chances of patients’ overall survival and will reduce cancer mortality.
Most patients will be familiar with direct visualization procedures and imaging techniques because these are procedures that are performed on a patient.
Direct visualization procedures include procedures such as when a physician inspects an organ, such as colonoscopy or endoscopy for gastrointestinal tumors, or a pelvic exam for cervical cancer. These techniques tend to have the highest performance for detecting early cancers, because the physician has direct access to the tissue being investigated. But these procedures are often uncomfortable, time-consuming, and invasive.
Imaging techniques include all of the methods physicians use to try to get a picture or a movie of what is going on inside the body. Most patents will be familiar with the names of these techniques, even if they may not be familiar with how these imaging techniques work. In general, these imaging techniques either have good performance characteristics and a hefty price tag (MRI, CT and PET), or lower performance characteristics at a lower cost (ultrasound and mammogram).
Patients tend to be less familiar with in vitro diagnostic tests. These are tests where a physician will take blood or tissue samples from a patient for analysis. For cancer diagnosis, physicians have previously needed to remove a section of tissue from a patient’s tumor, usually through a biopsy, in order to determine if the tumor was malignant or benign and to get more information about the tumor. However, biopsies are invasive, may induce complications and depending on the tumor location, are not always feasible. For cancer screening and monitoring, physicians have traditionally relied on protein tumor markers, such as PSA for prostate cancer. Unfortunately, protein tumor markers are seldom elevated during the early stages of cancer, and often have a false positive rate that makes them unreliable tools for cancer screening.
Physicians use a combination of these methods to try to identify cancers as early as possible. The earlier a cancer is detected, the more likely a patient can be cured. If cancers are caught late, there are far fewer treatment options, the treatment options available often have severe side effects and curative treatment becomes far less likely.
Medgadget: How will the IvyGene tests help in this context?
Van Etten: Over the last decade, new tools have been developed that allow us to detect and analyze DNA that is shed from tumors into the blood stream. These kinds of tests, which are often referred to as liquid biopsies, allow us to get information about tumors that used to require a tissue sample.
Many tests that are on the market or are in development look for mutated DNA in the blood. Such tests have been shown to be useful mainly as companion diagnostic tests, which are tests that are used for selecting what type of therapy should be used to treat patients who have already been diagnosed with cancer. However, these types of DNA mutation-based tests have tended to perform poorly when used for cancer screening or diagnosis. This is because not all DNA mutations indicate that cancer is present, and not all cancers will have the same set of DNA mutations. In addition, these genetic biomarkers usually vary from case to case, which makes the development of sensitive and generalizable approaches challenging.
In contrast, the IvyGene tests look for DNA methylation markers. DNA methylation is an epigenetic marker. This means that DNA is either methylated or not methylated at specific places in response to what genes are being turned on or turned off within a cell at any given time. Because certain genes are almost always turned on or turned off when a cell becomes a cancer cell, measuring DNA methylation at particular sites within DNA is a very accurate method to distinguish a cancer cell from a normal cell. And when asessing DNA methylation of the DNA within blood samples, this approach has also been shown to be an accurate method of detecting cancers, monitoring tumor burden and even determining what type of cancer is present.
Medgadget: So, when will people undergo this type of testing? Is this intended for routine screening, or for use in situations where cancer is already suspected?
Van Etten: Because of the versatility of this kind of test, the IvyGene tests may be used in a number of different situations.
Initially, we envision that physicians will recommend that patients who are at high risk for certain cancers to take an IvyGene test. Physicians may also use these tests to monitor patients who are either undergoing treatment for an active disease or patient who have completed treatment in order to detect a cancer recurrence as early as possible.
But within the foreseeable future, it is very possible that most of the current cancer screening procedures will be replaced with highly accurate and non-invasive DNA blood tests, like the IvyGene tests.
Medgadget: Please give us an overview of the science behind the tests. How long has this technology been around?
Van Etten: DNA methylation is a type of epigenetic modification that plays key roles in gene expression and cell differentiation. Since DNA methylation plays such an important role in gene expression, researchers have conducted many studies examining the association between alterations in methylation patterns and diseases such as cancer.
In general, when a gene is turned off, then the control regions of a gene will be extensively methylated. But when a gene is turned on, then these same control regions of the gene will not be methylated. This means that just by examining where DNA is methylated, you can tell what genes are turned on and what genes are turned off.
When a cell becomes a cancer cell, certain genes are turned on and certain genes are turned off, which alters the DNA methylation patterns of the cancer cell DNA. These changes in DNA methylation happen very consistently in cancer cells – far more consistently than any DNA mutation. This means it is possible to tell if a cell is a cancer cell or a normal cell just by looking at where the DNA is methylated.
Both normal cells and cancer cells shed DNA into the circulation. So, by drawing blood from a patient, extracting the free-floating DNA from the blood and then determining where this DNA is methylated, it is possible to detect DNA that is shed from cancer cells at an early stage of the disease.
Scientists have been studying DNA methylation since the 1940s. However, there have been two very big technological breakthroughs recently. First, the techniques used to extract DNA and determine where it is methylated have been refined to the point that it is now possible to very accurately measure DNA methylation in blood samples by using very small amounts of DNA. Second, major advances in DNA sequencing and machine learning approaches now allowed us to analyze huge data sets in order to identify the DNA methylation patterns that indicate cancer presence.
These two advances, when combined with LAM’s large biobank of samples, has allowed LAM to develop non-invasive, DNA methylation-based tests at a pace that has previously been unheard of in the biotechnology industry.
Medgadget: So, how will a patient go about getting tested? What will be involved for these tests, and how long will it take to get the results?
Van Etten: All cancer testing should start with a patient speaking with their physician. Medical professionals are trained to identify which patients will benefit from testing, and also to interpret the patient’s results and recommend any follow-up procedures.
For the IvyGene tests, a patient’s physician will be able to order the test for them. Then the patient will just need to undergo a normal blood draw and the blood samples will be shipped to a laboratory for analysis. The results of the test will be sent to the requesting physician within 5 business days.
Medgadget: How accurate will these tests be?
Van Etten: We are developing our tests to have the highest performance characteristics possible. For most of the tests we have in development, we have been able to show that DNA methylation-based tests can be both more than 90% sensitive (the likelihood that a test will be positive when disease is present) and more than 95% specific (the likelihood that a test is negative when disease is not present).
Most blood tests on the market today only have a high sensitivity or a high specificity, and physicians use these tests in certain circumstances in order to attempt to rule-in or rule-out a diagnosis. It is very rare for a blood test to have BOTH high sensitivity and specificity. Tests with these kinds of exceptional performance characteristics are what we believe will allow physicians to detect cancers at an earlier stage, which in turn will save a great many lives.
Medgadget: What are your future plans for this technology?
Van Etten: Today we have been speaking about using DNA methylation for cancer detection. But DNA methylation testing can do much, much more. For example, it has been shown that DNA methylation can be used to identify what kind of cancer is present, and how aggressive the cancer may be. Tests that can provide this kind of information to patients and physicians can help to guide treatment decisions, and ultimately improve patient outcomes.