Even as cancer researchers toil throughout the year to bring about a ray of hope in the lives of patients and their caretakers, Epigeneres Biotechnology Pvt. Ltd based in Mumbai, India and Singapore-based Tzar Labs have developed a novel blood test - the HrC test that can not only detect the presence or absence of cancer but can also rule out the possibility of having one in the following year.
In their path-breaking research, Dr Vinay Kumar Tripathi, Mumbai based nanotech scientist, and his sons Ashish Tripathi (CEO, Tzar labs) and Anish Tripathi (COO, Epigeneres) have been involved in developing this very promising endeavour which can also detect cancer early. The name HrC stands for “Himanshu Roy Cancer Test”, and is dedicated to their brother-in-law, the late Himanshu Roy, IPS, who died from causes linked to this disease
While there are many causes for the onset of the disease, here we wish to highlight late diagnosis. Most cancers are diagnosed at the third or fourth stage which leaves the patient with minimal treatment options and chances of survival. Tissue and liquid biopsies are frequently utilised to detect the presence of cancer. The former is more invasive and can aggravate the tumour condition if present. Liquid biopsies are non-invasive and show the presence of circulating tumour DNA in the blood.
CSP was in conversation with the Tripathi brothers who spoke about the test and its efficacy and the cancer research scenario in India. “This test will be affordable and the cheapest in India, as compared to in any other part of the world. This test will also get launched in India first, possibly before the end of this year itself ,” they said. They write in a Scientific Journal that "HrC method is a novel breakthrough, non-invasive, blood-based diagnostic tool that can detect as well as classify solid tumors, hematological malignancies and sarcomas, based on their stage."
Can you tell us about the research journey and how you arrived at the breakthrough?
We have been focusing on molecular medicine for over eight years now, and particularly investigating the potential impact of pharma and nutraceutical molecules on gene markers. Our father, Dr. VK Tripathi, a nanotechnologist, deeply believed that molecular medicine would be the most disruptive force in health sciences over the next few decades. In the process of looking for a technology that could test and verify the impact on certain gene markers, we came across the existence of VSELs. These cells had been discovered more than two decades back, but only been isolated from tissues. We were able to isolate these cells from the blood, and also got great results on gene markers. Ashish then realised the potential of this technology in the area of diagnostics, particularly early-detection of cancer. Our 1000-patient clinical study was then able to prove this conclusively, and we then decided to get a paper published on this study. It is our honour that we have been able to get our peer-reviewed paper published in SCRR (Stem Cell Reviews and Reports), a globally reputed science journal, part of the Springer-Nature group, Germany (Quest for Pan-Cancer Diagnosis/Prognosis Ends with HrC Test Measuring Oct4A in Peripheral Blood | SpringerLink).
The basic premise of our discovery is that cancer gets triggered only when certain underlying genetic mutations have occurred, and this happens much before creation of tumour/cancer stem cells, let alone tumour formation. Our gene markers can detect these genetic mutations, and hence identify cancer at a very early stage.
Anish Tripathi (COO, Epigeneres)
Ashish Tripathi (CEO, Tzar Labs)
How does this differ from the other liquid biopsy tests and why do you think this is better?
Tissue biopsy is known to be harmful in itself, as it is an invasive diagnostic procedure where a needle is inserted into the body and cancer tissue is extracted. Liquid biopsy tests rely on finding circulating tumor cells or tumor DNA to detect cancer in the blood. While these tests are a need of the hour and some of them have been commercialized, they are usually time consuming, expensive, cumbersome, and have low sensitivity and specificity. This test exhibits low accuracy in terms of enrichment of DNA fragments or circulating tumor cells, and can easily and accurately only detect late-stage cancers. For early-stage cancers, it is prone to erroneous results, mainly false negatives. As mentioned in our published paper, the HrC test circumvents all these issues, and is highly accurate.
How long did it take to develop this test?
Well, one can say that it took around three years to develop the diagnostic test, but it needed our father’s 8 years of research preceding that on molecular medicines to stumble across this test. More importantly, the only reason we were able to look farther than others, is because we were standing upon the shoulders of giants who dedicated decades to the study of stem cells, particularly Prof. Dr Mariusz Ratajczak of the University of Louisville, and Dr. Deepa Bhartiya of ICMR-NIRRH.
What were the challenges you faced during the development?
One of the main challenges was the fact that there was a strong debate going on in the global scientific community about the very existence of VSELs, with both sides having taken hard positions. For us it was very clear that the proof of the pudding was in the eating. We were not only able to see these cells (we have photographic evidence), but were also able to isolate them from blood, and provide a strong practical application in the area of early detection of cancer. The other challenge was to keep the whole process under wraps, until all patents had been filed and the clinical trial had been successfully completed. We did not want to jump the gun and claim the discovery without foolproof evidence, and having a peer-reviewed published paper in place.
I would also like to add that this is a common mistake made in Indian institutions. We are aware of one particular case where a gene marker was discovered by one of our leading institutions, but the credit went to China who found a practical application of the marker for diagnosing Head & Neck Cancer. It is important to have a clear plan on your discovery, i.e., conducting trials, identifying the innovative steps, and then patenting it; while not just being in a hurry to publish.
How is this test going to affect treatment strategies?
This test can become an invaluable adjuvant to existing radiological tests that Oncologists are used to. This can also reduce the number of times that tests like PET and CT need to be done, because they are harmful in themselves. This can also reduce (not eliminate) the need for performing biopsies, which are not only invasive, but can also trigger increased activity within the tumour and hasten metastasis.
The most important impact of this test on treatment strategies would be the frequency, non-invasiveness, and harmless manner in which Oncologists can get feedback on a treatment protocol. Knowing whether the cancer is in progression, regression, or remission, based on the protocol being followed, is the most important and basic piece of information that an Oncologist requires. One can now get this information as often as required, through a simple blood test.
What is an HrC marker?
HrC is a proprietary algorithm developed by our scientists from certain transcriptomic markers that we are able to get from cells isolated in peripheral blood. It is a first-of-its-kind patented non-invasive 'HrC' test (NIHT), the effectiveness of which we have shown through meticulously conducted clinical trials. It is a common scale for both cancer patients as well as non-cancer subjects, which indicates the status on a continuum of cancer absent, imminent, or present; and if present, the stage of cancer as well.
The name HrC stands for “Himanshu Roy Cancer Test”, and is dedicated to our brother-in-law, the late Himanshu Roy, IPS, who died from causes linked to this disease
Will the test also recognize other cancer markers that are associated with a specific type of cancer?
At this point, the test is focused on a single, unique, biomarker that is associated with detection of all types of cancer, including solid tumors, hematological malignancies and soft tissue sarcomas.
In time, our more comprehensive test, the Transcriptomic Analysis Report, will provide information on all types (specific and generic) of cancer and non-cancer biomarkers, and allow for what is known as an “all organ biopsy”, from the same blood test.
Can this test be taken up by a cancer survivor too to eliminate the possibilities of a relapse?
One of the biggest benefits of this test will be for cancer survivors, who walk away from a cancer remission in the hope that it will not recur. Oncologists say that if cancer does not reappear in around 8 years’ time, then the risk of recurrence drops dramatically. However, it is known to recur even after 10-15 years. Recurrence is most tragic, as more often than not, it gets discovered in late stages, when it has metastasized, and chances of survival are extremely poor. This is also because the standard tests for recurrence are radiological, and tumours can be missed particularly in early stages.
When this test becomes ubiquitous, an annual blood test will be the most effective way to monitor any relapse, and the moment HrC scores go into the dangerous zone, tumours can be radiologically tested, and treatment can start. This test will be a boon for cancer survivors.
What can you tell us about the cancer screening scenario in India? And how, in your opinion, can it improve? (Early diagnosis equals early treatment)
Oncologists know that all cancer survivors carry the risk of recurrence, and advise that they get annual checks done. Most cancer survivors in turn, do follow this advice. However, the bitter truth is that most recurrences get caught by accident during non-routine examinations, like x-rays, sonographies, etc. It's only late-stage cancers that show overt symptoms like severe pain, etc.
The cancer screening scenario in India is no different from anywhere else in the world, hamstrung by a lack of appropriate early-detection technologies, rather than a lack of facilities or effort. We hope that the HrC test will fill this gap permanently.
What is the standard number of VSELs present in a cell and how much does it vary in a diseased state?
VSELs are rare circulating stem cells in the human body. Their number is approximately 670 cells per milliliter of blood in normal individuals according to a recent scientific study, and increases depending on infections, inflammation, or diseases, which are all active triggers. Cancer is a hyper-inflammatory disease, and hence the number of VSELs mobilized in the bloodstream in this case is extremely high, thus delineating it sharply from all other conditions. Our HrC test scale captures this hyper-mobilized level of VSELs very accurately.
Other than Oct4a, were there any other factors that expressed differently?
Yes, there are other factors expressed differently, besides Oct4a. Our HrC test score algorithm is a triangulation of at least three markers. However, this information is proprietary, and therefore not disclosable for now.
How rapid are these tests?
The HrC test at present can take 3-4 days for results to be obtained, post blood sample submission. However, with our proposed automation, we should be able to reduce this to delivering the report in 2 days.
Can you tell us about the collaborations inside and outside of India while developing this test?
We have not formally collaborated with any entity, besides the two entities involved in co-developing this technology, i.e., Tzar and Epigeneres. Although, as mentioned before, we have depended on pioneering research done by many people in the area of VSELs and stem cells. We have also received significant assistance while conducting the clinical study from Avinash Cancer Clinic (Pune), Sanjeevan Hospital (Pune), ICMR-NIRRH (Mumbai), NFB (Mumbai), ACTREC (Navi Mumbai), and a host of other independent consultants and Oncologists.
In terms of cost, how affordable would this test be?
Since regulatory approvals are currently being obtained, and costing/pricing issues are being discussed, we cannot indicate the final pricing for the tests in India. However, this test will be affordable and the cheapest in India, as compared to any other part of the world. This test will also get launched in India first, possibly before the end of this year itself.
How accepting do you think this test will be across the globe considering the debate on VSELs?
The acceptance of the HrC test is not a mere academic debate on the existence of VSELs, to be agreed upon by the scientific community. In our minds, this debate has been long settled in favour of VSELs, because we have seen the evidence, and even photographed them. The acceptance of our test will be decided by Oncologists, when they realize the invaluable assistance that the HrC score can provide in making treatment-related decisions. This can potentially save lives. Once the test is accepted by Oncologists, it is only a matter of time that the test will become ubiquitous across the world.
Even from a regulatory perspective, we do not see a huge challenge. The first principle of any new medication or diagnostic tool is that it should not do any harm, even if it does not do any good. If there is potential for harm to humans, the regulatory framework is rigid and hard, and rightly so. The HrC test is non-invasive, and there is nothing being put into the body, only a small sample of blood being drawn. In this case, the potential for harm is next to zero. The insights and the information we can draw from the blood, and the benefit that it can provide, will obviously prompt regulatory bodies to grant approvals without much concern.
What can you tell us about the cancer research scenario in India and how can it be improved?
The Indian cancer research arena is really exciting today, especially with the advent of modern advanced genomic and imaging technologies and tools to diagnose cancer. We would like to improve it by providing a standalone blood test that can aid Oncologists, Clinicians and Scientists in furthering evidence in detection of cancer and its stages, especially catching it at an early stage.
Indian research talent is recognised to be amongst the best in the world. We believe that the HrC test can provide a new direction to cancer research. It can also provide a much quicker and less harmful method of clinical trials for new medicines and treatment protocols, as the feedback mechanism is much faster, accurate and robust.