Blog: Priya Gogoi

It's a feel-good storyline: Start-up founders lacking moola to enter business plan competition volunteer instead, return next year to win Best New Business Idea award at the GLEQ contest. Priya Gogoi, co-founder of DeNovo Sciences, covers the partners' de novo strategies for business launching and development of a cancer cell detection tool.

Post 3: Children of the Dark Lord

A common complaint we so called "tech" people often come across is that we are not coherent to the lay person. During our business presentations, people get lost amid the explanation of the core technology. I am not immune to it, either. When the subject matter is outside my scope of understanding, presentations rush past my head – seriously. So today I am going to tackle a difficult biotech subject that DeNovo Sciences is working on and try to make it interesting. You may have known from my previous articles that DeNovo Sciences is developing a cancer diagnostic platform that aims to replace painful biopsies. I feel that the general public should be aware of this technology as it has the potential to affect all of us in some way or other. So get ready to listen to the story starring circulating tumor cells.    

This is a story that involves a battle where the battlefield is within our body. As in any other epic, there is a good side and there is an evil side. The good side is composed of our immune system containing our white blood cells as the ever vigilant soldiers, protecting our body, the fortress, from enemies like viruses, bacteria and other bad germs that attack from outside. But the villain I am going to talk about is even more sinister because it is raised in our own home by our own flesh and blood. Yes, I am talking about tumors. This bloody mess of a villain resides in our organs and waits till its progeny can raise their own wicked colonies. And the real danger lies in that. Once the sons and daughters of the dark lord, let's call him the "Primary Tumor", establish their own kingdoms, it is a downhill battle for our defense system. These children of the dark lord sometimes pass into the blood stream where they are known as "circulating tumor cells" (CTCs for short), and this story is about them.

Even though all the CTCs present in the blood stream originate from the dark lord, not all of them are equally evil. Surprisingly, CTCs born from the same primary tumor display a wide spectrum of heterogeneity in their genetic (hereditary) as well as phenotypic (looks department) make-up. Most of the CTCs are actually harmless and undergo planned suicide as soon as they are released into the blood stream, the process known as apoptosis. Some of them however, linger on and shape-shift from their original form by losing their older clothes or surface markers in a process called epithelial-to-mesenchymal transition, or EMT. These are the CTCs that are the most dangerous and are now known as cancer stem cells capable of invading distant organs and raising their own evil empire. Once they identify a suitable place to invade, they once again shape-shift in a process called mesenchymal-to-epithelial transition, or MET.

After this process they are no longer children; they become their own form of dark lords, now known as "secondary tumors". These secondary tumors are even more aggressive than their predecessor and do not rest until they multiply vigorously by destroying everything in their path. At this point the body is fighting a losing war and the defense system is left in tatters. According to experts, the cancer has now metastasized. Hence, capturing these CTCs and characterizing them into their harmless and aggressive forms is crucial for the survival of cancer patients.

For a long time, these rare CTCs were difficult to detect as they hid among the millions of white blood cells, who looked almost the same size and shape as the former. Making the task more even difficult is the presence of billions of red blood cells; the oil that keeps our machine (the heart) running. But the advent of modern technology might change this scenario. Scientists have been trying many different approaches to capture these dark seeds, as they might hold in them the secrets of metastasis.

Some have tried to capture these CTCs based on their surface markers or their outer clothing, as I have mentioned earlier. However, depending on just one single marker is a flawed approach as these cells are capable of shape-shifting. Hence, another approach is desired where multiple markers can be combined to maximize the chances of their capture. One of the simplest techniques to capture these rare cells is to use a filter device and separate the various entities based on their size. Size is indeed a good selection marker, because cancer cells are usually bigger than the other cells. However, the size differences are in the micrometer scale (think really small, smaller than a grain of sand) and simple sieve devices are not sophisticated enough to distinguish between the CTCs and our loyal soldiers.

DeNovo's technology involves the development of a microfluidics device (an advanced micro-scale filter device) that can separate these elusive cells in their own prisons, where various interrogation techniques can be applied on them to reveal their secrets. The chip provides a flexible platform, where multiple markers (up to five) can be tested simultaneously to force these cells into submission.  

What are the implications of this technology and how does it influence our story? To date, hundreds of thousands of people die of cancer every year in the U.S. alone. Most of us might be aware of at least one person who has suffered the trauma of cancer. It is interesting to note that 90% of these deaths are due to metastasis, or the spread of the cancer, to multiple distant sites in the body. On a more personal note, we all know that the saddest part of this malaise is the suffering it brings to not only the patient but to everyone who loves that person.

On top of that suffering, now imagine the additional pain of a big needle piercing your loved one to confirm the stage of cancer; in technical terms this procedure is called biopsy. Biopsies are also costly and carry the risk of spreading the cancer further by spreading the children of the dark lord – the primary tumor – further. Detecting these evil seeds directly from a blood draw can alleviate the pain of cancer patients to a great level. DeNovo's CTC detection technology thus provides a painless alternative to agonizing biopsies. Furthermore, DeNovo's technology also provides a vindication to our heroes, the white blood cells. By providing a platform where scientists can differentiate side by side the soldiers from the similar looking CTCs, Denovo Sciences is giving the good side a leg up!