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Inside a tumor, cells are constantly growing, multiplying and dying. When cancer cells die, they leave behind clues that are transforming scientists understanding of the disease. Dying cancer cells breakup into microscopic bubbles which can contain all sorts of molecules including chunks of the cells’ DNA. When cancer cells die close enough to a tumors’ blood supply, these DNA-filled bubbles can enter the bloodstream. And as they break down, the tumor DNA is released. This means it can be isolated from just a simple sample of blood.
The researchers are now using the DNA is patient’s blood samples to learn more about cancer. That’s because the revealer snapshot of the different genetic vaults fueling a tumor’s growth and how they change as it responds to treatment. Scientists want to use this to develop so-called ‘Liquid Biopsies’ to help doctors monitor how a patient’s tumor is responding to treatment. For example, if a blood sample shows signs of tumor DNA after treatment; it could mean the patient needs a scan earlier than planned. Or, if new faults are spotted in the DNA, this could help doctors rapidly switch to treatments tailored to these changes. Ultimately, this could open up new ways to personalize each patient’s care and help their doctors stay one step ahead of the disease.
Here is a patient with a skin cancer called Melanoma. It’s horrible, the cancer has gone everywhere. However, the scientists were able to map the mutations of this cancer and be able to give a specific treatment that targets one of the mutations. And the result is almost miraculous. Tumors almost seem to melt away. Unfortunately, this is not the end of the story. A few months later, this picture was taken. The tumor has come back.
The question is, why? The answer is tumor heterogeneity. Even a cancer as small as 1cm in diameter, harbors over a 100 million different cells. While genetically similar, there are small differences in these different cancers that make them differently prone to different drugs. So even if you have a drug that’s highly effective, that kills almost all the cancer cells, there is a chance that there is a small population that’s resistant to the drug. This ultimately is the population that comes back, and takes over the patient.
So then the question is, what do we do with this information? The key then, is to apply all these exciting advancement in cancer therapy earlier, as soon as we can, before these resistance clones emerge. The key to cancer and curing cancer is early detection. And we intuitively know this. Finding cancer early results in better outcome and the numbers show this as well. For example, in ovarian cancer, if the cancer can be detected in stage 4, only 17% of the women survive at five years. However, if you are able to detect this cancer as early as Stage 1, over 92% of women will survive. But the sad fact is, only 15% of women are detected at Stage 1, whereas the vast majority, 70% are detected in stages 3 and 4. We desperately need better detection mechanisms for cancers.
The current best ways to screen cancer fall into one of three categories. First, it’s a medical procedure which is like colonoscopy for colon cancer. Second is protein biomarker, like PSA for prostate cancer. And third, imaging techniques, such as mammography for breast cancer. Medical procedures are the gold standard; however they are highly invasive and require a large infrastructure to implement. Protein markers, while effective in some populations, are not very specific in some circumstances resulting in high numbers of false positives; which then results in unnecessary work-ups and unnecessary procedures. Imaging methods, while useful in some populations, expose patients to harmful radiations. In addition, it is not applicable to all patients. For example, mammography has problems in women with dense breasts.
So what we need is a method, that is non-invasive, that is light in infrastructure, that is highly specific, that also does not have false positives, does not use any radiation, and is applicable to large populations. Even more importantly, we need a method to be able to detect cancers before they are 100 million cells in size. Does such a technology exist? The answer is, YES. Scientists at John Hopkins have developed a technology which can detect cancer with a simple blood test. Central to this technology, is a simple blood test. The blood circulatory system, while seemingly mundane, is essential for you to survive, providing oxygen and nutrients to your cells, and removing waste and Carbon dioxide.
Here’s a key biological insight. Cancer cells grow and die faster than normal cells, and when they die DNA is shed into the blood system. Since we know the signatures of these cancer cells from all the different cancer genome sequencing project, we can look for those signals in the blood to be able to detect these cancers early. So instead of waiting for cancers to be large enough to cause symptoms, or dense enough to show up on imaging, or prominent enough for able to visualize on medical procedures, we can start looking for cancers while they are relatively pretty small by looking for these small amounts of DNA in the blood. So, how the scientists do this?
First, they start-off with a sample of blood test; no radiation-no complicated equipments. Then they extract the DNA out of it. While the body mostly has healthy cells, most of the DNA that’s detected will be from healthy cells. However, there will be a small amount (less than 1%) that comes from the cancer cells. Then the molecular biology methods are used to be able to enrich this DNA for areas of the genome which are known to be associated with cancer. This enables to put this DNA into DNA-sequencing machine to digitize the DNA into A’s C’s T’s and G’s. Then comes applying statistical and computational methods to be able to find the small signal that’s present, indicative of the small amount of cancer DNA in the blood.
So does this actually work in patients? Well, because there is no way of really predicting right now which patient will get cancer, they use the next best population: cancers in remission, specifically lung cancer. The sad fact is, even with the best drugs that we have today, most lung cancers come back. The key then, is to see, whether we are able to detect these recurrences of cancers earlier than with standard methods. Here’s an example of one patient who undergoes surgery at time point zero, and then undergoes chemotherapy. Then the patient is under remission. He is monitored using clinical exams and imaging methods. Around day 450, unfortunately, the cancer comes back. The question is, are we able to catch this earlier? During this whole time, the blood have been collected serially, to measure the amount of ctDNA in the blood.
So, at the initial time point as expected, there’s a high level of cancer DNA in the blood. However, this goes away to zero in subsequent time points and remains negligible after subsequent point. Around, day 340, there is a rise of cancer DNA in the blood. And eventually, it goes up higher for days 400 and 450. Here is the key, at day 340 the rise in the cancer DNA in blood has been seen. That means, this cancer has been detected before over a hundred days earlier than usual. This is a hundred days earlier that therapy can be given, a hundred days earlier the surgical intervention can be initiated. For some patients, this “hundred days” means the matter of life and death.
We cherish a dream, that one day from two vials of blood we will be able to compare the DNA from all known signatures of cancer and hopefully then detect cancers months to even years earlier. Even with the therapies we have currently, this could mean that millions of lives could be saved. And if you add onto that, recent advancement in immunotherapy and targeted therapies, the end of cancer is in sight. The next time when you hear the word “cancer”, I want you to add the emotions “hope”. Cancer researchers around the world are working feverishly to beat this disease and tremendous progress is being made. This is the beginning of the end, we will win the war on cancer.
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