Cancer is a dreaded term in most families. Across the globe, annually about 8 million people die of cancer. In USA alone, every year about 40,000 women die of breast cancer. Mammograms are the best test, yet they often produce false positives, which can warrant unwanted biopsies and surgeries. So called, “high-risk” lesions have abnormal cells and patients are advised surgery. About 90% of the time, the lesion is benign and surgery is an expensive and painful wasted exercise. The final and inconclusive proof of the disease is tissue biopsy, a relatively painful process. In certain cases, the tumour is not accessible or the patient is very weak for biopsy. How then canoncologists confirm the presence of cancer?
The research related to cancer is predominantly on two major fronts – 1) to find drugs, and ways to treat cancer and 2) to detect cancer at a very early stage where the chances of recovery and remission high. Typically, people suspect cancer as the cause only when it manifests in some obvious and visible form. Nevertheless, often by then, the disease has progressed to an advanced stage – a stage beyond treatment. Can doctors detect them very early even before the person feels any symptoms? By detecting early, doctors can treat and save many lives and spare many people of anxiety and agony.
Can a simple blood testpredict, detect, and confirm the presence of cancer? Yes, for a few types of cancers it is possible. Colorectal Cancer (CRC) is one for which a blood test is available. Testing the blood for the presence of tumour cells and DNA is a non-invasive approach compared to the invasive biopsy, which is a surgery.
The concept behind it is as follows. Dying cancer cells shed DNA into a person’s blood and these are called circulating DNA or ctDNA. They can act as a non-invasive cancer biomarker. The amount of ctDNA is very small compared to the amount of healthy DNA in the blood. Nevertheless, if we can develop methods to detect this tiny amount, then identification of cancer at a very early stage is possible. Using a technique called high-intensity or ultrafast or next generation sequencing, fast computers and powerful software together, geneticists decode millions of these short strands of DNA in the blood. The software compares the results with the map of human genome and when it detects specific patterns of rearranged DNA, it identifies the presence of cancer. Today, this process is expensive because the machines cost upwards of a US $ one million per piece. However, with time, the machines will shrink in size and the test will become affordable.
This process of using blood to detect cancer is called as liquid biopsy. Dr. Dennis Lo of The Chinese University of Hong Kong (CUHK) pioneered this technique in 1997, which led to a safe test for detecting Downs Syndrome in the foetus by testing the pregnant mother’s blood. He is conducting a study of 20,000 people in Hong-Kong to check if nasopharyngeal carcinoma can be detected using liquid biopsy. The Epstein-Barr virus causes this rare form of cancer and is common among men in Hong Kong and South China. Dr. Lo has tested more than 10000 men, picked up 17 cases of cancer, 13 of which in stage 1 – a curable stage.
Recently, scientists from Edith Cowan University in Australia have developed a blood test to detect melanoma. They conducted a pilot study on a small group of people and the test detected early stage melanoma in 79% of the cases. Currently, melanoma is detected by the naked eye followed by a tissue biopsy.
The process needs only about 5 ml of blood, which is “spun down” to yield 2 ml of plasma, which is then analysed for tumour DNA and checked for mutations, chemical variations of the genetic strands, the size of the fragments, or a combination of these. Techniques are also available to detect ctDNA in urine and cerebrospinal fluid.
SOPHiA Genetics is a company that is using artificial intelligence to detect variants in genomic patterns with 99.99% specificity and sensitivity.
Grain Inc., a company in the Silicon Valley believes that with this technique, it can detect cancers early enough to be treated. It has raised US $ 1.1 billion from private investors and venture capitalists. It has a large number of ultrafast DNA sequencing machines each costing about a US $ 1 million. The company collects about 1000 GB of raw data from each patient’s blood sample. Along with this data, the patients’ medical records are fed into a software that looks for patterns. This process is expensive and time-consuming. It also needs many processors working in a massively parallel configuration, highly scalable and high-throughput distributed storage devices, very efficient databases and powerful bioinformatics software packages. While genomic data is exploding, cost of gene sequencing is also fast plummeting.
Liquid biopsy also offers many other benefits.Since the blood test reveals the sequencing, doctors can use a specific drug that is the best fit and thereby personalize the treatment. It can assist in tracking the progress of the tumour and the effectiveness of the treatment by drawing blood samples periodically. This is particularly important for solid tumours (by avoiding invasive biopsies) for it provides non-invasive access to malignant DNA. Liquid biopsy also gives comprehensive picture of the progression or remission of cancer. It is easy, quick and repeatable. For patients who cannot undergo invasive tissue biopsy, this is a boon. For example, pancreas is situated deep inside the abdomen and biopsy is a very complicated procedure requiring high precision.
However, liquid biopsy as a test to detect canceris in its early days and several questions need to be addressed. How does the accuracy of the test vary among different types of tumour, and stages of disease? What about the false-positives, which may lead to panic, stress and even treatments that are not required? Will the tests tell the doctor the location, the state (stage) of cancer and suggest types of treatment?In about a third of the types of cancer, the tumour does not shed adequate amount of DNA into the blood rendering liquid biopsy unviable.
With the global attention given to cancer because of escalating costs of treatment, researchers will find answers to many of these questions. This blood test holds a lot of promise and power that it may be a boon for cancer treatment, for early detection is the best.
– Dr. S. Chellaiah
Dr. S. Chellaiah is a professor of systems in Loyola Institute of BusinessAdministration (LIBA), Chennai and can be reached at firstname.lastname@example.org