Cancer, which touches the lives of many, has remained a leading cause of death in the United States. While most cancers are treatable if caught before it has become locally invasive and has spread through the body, many cancers are not diagnosed until it is “too late.” This difficulty faced by treatments certainly points to the need for early detection and diagnosis to improve cancer outcomes.
Ideally, cancer should be prevented through detection and removal of pre-cancerous lesions or growths before the cancer develops. Although this can be done now in some cases, like in the removal of pre-cancerous cells discovered by cervical screening or by removal of pre-cancerous colorectal polyps discovered on colonoscopy, it is the exception and not the rule.
Meeting an Urgent Need
What physicians need is an accurate, non-invasive, and low cost diagnostic test that is accessible and easy to use. The goal would be for this simple test to detect all the major common cancers at an early stage while distinguishing between them. Only a blood test could fill all these requirements, but such a test seems fanciful when the only commonly used blood test for the detection of cancer is still the PSA test for prostate cancer – a test that has been around for decades.
Blood tests are very useful for detecting things like elevated sugar levels or biomarkers which should not be in the blood of healthy people. Troponin, a protein released into the blood from damaged heart cells during a heart attack, or foreign virus particles are examples of these biomarkers. The problem is that cancer cells are not considered foreign in the body and will not usually cause gross changes in blood chemistry until the later stages of disease. Some cancers do release proteins that are not usually present in the blood but, except for PSA, these have not been useful for cancer detection because they generally do not show a high degree of sensitivity and specificity or they become too expensive.
Until recently, cancer was generally regarded as a purely genetic disease caused by mutations of oncogenes, which broadly promote uncontrolled cell proliferation, and tumor suppressor genes that broadly prevent the uncontrolled cell proliferation that is characteristic of cancer. A single mutation will not result in cancer, but if multiple gene mutations are acquired from carcinogens such as tobacco smoke, control of cell proliferation may be lost and cancer may develop. People unfortunately born with one or more of these mutations (for example, the BRCA gene mutation in breast cancer) are at higher risk of developing cancer.
Epigenetic Switches and Nucleosomes
It is now recognized that oncogene and tumor suppressor gene expression can also be turned “on” or “off” by epigenetic mechanisms, causing a revolution in cancer diagnostics. The normal cellular mechanism for switching genes on or off – for example, the mechanism which switches only brain protein genes on in brain cells, and not, for example, liver protein genes – is subverted in cancer to mis-regulate the switching of expression of oncogenes and tumor suppressor genes. These epigenetic switches are affected by chemical structures in the chromosomes, including the methylation of DNA and its associated histone proteins. Structural changes to the chromosome of cancer cells are greatly changed from those in healthy cells, due to the hijacking of the switching mechanism by the cancer. Moreover, these changes vary in different cancers and occur very early in the cancer disease – even earlier than the visible changes that are detected by the cervical smear test used for cervical cancer screening. This means that epigenetic changes in cancer cells can be used as biomarkers for the early detection of cancer and to differentiate between different cancers.
What makes these epigenetic changes useful for blood tests is that chromosome fragments, called nucleosomes, are present in every person’s blood as a result of normal cell turnover. In cancer patients, we have found through our extensive research that these nucleosomes “shed” from dead cancer cells circulating in the blood and retain their epigenetic structural changes, which can be detected. VolitionRx’s Novel Technology Building on this research, VolitionRx has developed its proprietary Nucleosomics platform technology to analyze nucleosomes circulating in a patient’s blood to determine early on whether a cancer is present and, if present, which cancer it may be. The Nucleosomics technology involves analysis of nucleosomes using a panel of simple ELISA blood tests called NuQ. In fact, to date VolitionRx has developed a suite of 20 NuQ ELISA tests for different epigenetic switching structures in nucleosomes in the blood. Following promising results in small early clinical studies focused on colorectal cancer (CRC), VolitionRx is now conducting larger studies, including a study of approximately 4,800 patients referred for colonoscopy for symptomatic reasons in collaboration with Hivdovre Hospital in Copenhagen, Denmark. Interim results from the first approximately 1,000 of these patients have shown that a panel of NuQ tests correctly detected 84% of CRC cases, with a false positive rate of 22%. Importantly, early stage (stages I or II) CRC disease and 60% of pre-cancerous polyps were also detected. These findings will be confirmed when analysis of all 4,800 patients is complete and through a further 14,000-subject screening study.
Potential of the NuQ Blood Test for Early Cancer Detection
VolitionRx has also completed pilot studies for several additional cancers to determine if cancers other than CRC can be detected using our NuQ blood tests and whether a panel of NuQ® tests can differentiate these cancers from CRC. The results for prostate cancer in a small numbers of patients showed that 80% of prostate cancers were detected and that the epigenetic structures present in the blood nucleosomes of prostate cancer patients were different to those present in CRC patients, and that the two cancers could be distinguished on this basis. To investigate this further, VolitionRx recently announced its first US clinical study in prostate cancer with MD Anderson Cancer Center to assess the ability of VolitionRx’s NuQ test to distinguish anaplastic prostate cancer, a particularly aggressive form of the disease, from typical castration-resistant prostate cancer (CRPC), a less aggressive form.
While these are just two types of cancer, they are two of the most prevalent in the world. We are highly encouraged by the findings to date which demonstrate that a high level of accuracy and early detection is possible using our unique technology. We hope to also broaden our research into additional cancer types as identification of the most common major organ cancer diseases would represent a major medical advancement. To this end, VolitionRx is planning to conduct a clinical study next year in collaboration with Bonn University Hospital in Germany to investigate the nucleosome profiles of the 20 most common cancer diseases in about 4,000 patients. We remain very encouraged by the data thus far, are extremely proud of the work we continue to conduct to advance our NuQ technology, and look forward to sharing additional study results as they become available.