Molecular Profiling Wheels the Onco Revolution

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Dr Anurag Mehta, Director, Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, recently visited the US to get a glimpse of the oncology revolution. He shares his account with Shahid Akhter, ENN

You have visited the Star Health partner institutions in the US, including Yale and Thomas Jefferson? What’s your impression about their foray into medical research and technology?
Star Health has built a Medical Gateway that provides medical expertise and best practices in healthcare delivery from various hospitals in the United States to patients and hospitals internationally. Both Yale and Thomas Jefferson are top notch hospitals. US News & World Report this year named Jefferson University Hospital as among the best in the nation in several specialties.
Smilow Cancer Centre, a Yale University affiliate, is reckoned as a national leader in cancer research and treatment. Here, the best minds in medicine develop new therapies and detection strategies. These institutions are recognised for excellence in both, research and clinical care.
In the US, the diagnostic approach is laudable. There is concretisation of the process of molecular diagnostics through extensive validation and quality assurance programmes. In addition, what I found throughout was multi-gene tumour profiling being used more and more often. This is being used for prognosis, predicting response to therapy and most importantly for identifying the targets for precision medicine.

What exactly is molecular tumour profiling (TP) technology and how does it impact cancer diagnosis and treatment?
Cancer is a characterised by cells that have genes gone awry. These cancer cells, originating within tissues are immortalised and proliferate uncontrollably. They simply refuse to respond to signals that command normal cell growth and death. Over time they acquire attributes which allow them to breach anatomical barriers and spread (metastasize) to other sites of the body.
The current strategy to treat cancer is to morphologically type it using features elucidated under the microscope assisted by some auxiliary testing. This organ and morphological based tumour typing, lumps together a wide variety of genetically heterogeneous tumours. This is the reason why different people respond differentially to chemotherapy. The best way of course will be to type tumours based upon their genetic alteration(s). This is where the tumour gene profiling steps in. It is a test that checks all possible genes that can go amiss in a particular cancer type and prepares a profile of genetic signatures and hence the name “Tumour Gene Profiling.”
These molecular differences within one cancer type allows better determination of prognosis, predicting response to treatment and for therapy specific to the identified genetic lesion, the form of treatment we now call personalized / precision medicine and is the newest strategy to treat cancers. This test has been available in the US for past three years but, has been introduced in India just five months back.

Given the cancer burden of India and our existing healthcare resource and response, how fruitful do you think our partnership with Star Health will be?

Cancer burden is on the increase and so is cancer research and treatment. In days to come cancer treatment may become easier and doctors will have greater confidence in dealing with the deadly cells.
In India, besides traditional testing, we do carry out single gene analysis, ie sequential testing for possible mutated genes starting from the one most likely to alter to the lesser ones. This method though contemporary is time consuming, sample inefficient and in many cases costly when a rare genetic alteration happens. Comparatively, multiple gene analysis is a high-end profiling platform where all relevant genes are explored in one go (single analysis). It saves time, is tissue efficient and tissue does not become a limiting factor to successful diagnosis and hence to the most appropriate treatment. Soon it will be the elemental strategy to diagnose and treat cancer using best evidence based practices.
Partnership with Star Health paves the way to get the state of art available today. In India, we are good at managing cancer but when it comes to advanced diagnostics, we need to catch up especially in field of next generation sequencing and bioinformatics. Even if we import the technology overnight, we need to train the manpower in these aspects of molecular diagnostics. Additionally, a string of issues like validations, quality assurances, accuracy of results, etc are also concerns at present. Most importantly, if you have a result that is falsely negative, then the patient is deprived of potential benefits of a very useful targeted therapy. On the other hand, if the outcome is falsely positive then the patient pays unnecessarily for drugs that may harm him.

Once these mutations are precisely exposed, do we have the relevant drugs to target them? Can we call this precise and personal medicine?
Yes; this is the concept of targeted or personalised medicine. The concept invokes identifying the prime genetic change and using drugs to nullify its harmful effects. Today there exists more than a dozen of drugs to take care of possible genetic targets like erlotinib, gefitinib for EGFR mutations; herceptin and lapatinib foe Her2 amplification and , crizotinib for alk rearrangement. There are more and they are changing the landscape of treatment in these situations. Nearly 200 or more molecules are in various stages of development. Some are in clinical trials.

Are there any successful case study that has been initiated at RGCC via Star Health collaboration and how about the expense factor?
So far we have taken up seven cases in collaboration with Star Heath and they are all doing well. More cases are lined up.
As of today it may be a bit worrisome to pay 3750 USD but again you are getting the state of art without travelling to the US. Even if you go to US, you will end up paying more for the same tests. Molecular profiling is not just a sure and better way of diagnostics but there are so many other benefits too. It leads to improved quality of life, less cost on supportive treatment, hospitalisation is reduced or not required at all.

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