Translational research and treating resistance

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Published: 29 Mar 2017
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Dr Asima Mukhopadhyay - Tata Medical Centre, Kolkata, India

Dr Mukhopadhyay speaks with ecancertv at EBMCI 2017 about the patient journey to and through cancer treatment in India.

She summarises the educational and international background of patients seeking treatment at Tata Medical Centre, and goes on to consider how liquid biopsies can streamline HPV screening services.

Dr Mukhopadhyay also describes the challenge of treating radioresistant advanced cancers, with consideration of the potential benefits of adjuvant chemotherapy, and the need for further investment in integrated clinical research.

To start off with, we know that in India we have 68,000 women dying of cervical cancer each year. I think the majority of them are because they are presenting late and that goes down to a deep-rooted problem of the social and cultural structure of the country, education and whether women are free to come out with their symptoms and if they do actually know that these are the symptoms which are normal or abnormal. So these are the main things. The other thing we need to know about the centre, that it is not only a tertiary centre for India but also we have a lot of patients coming from neighbouring countries – Bhutan, Nepal and a big number of patients coming from Bangladesh which we have a theoretical advantage for the language because we speak the common. But that also brings up a lot of complex presentations we get. One of the other things we get because of the medical profession is an inadequate treatment. So many of the patients would have been misguided or half-treated with inadequate histology, coming to us and then the treatment like a book – early stage you do surgery, late stage you do radiotherapy - that does not apply any more. So for each and every case, depending on what the family has gone through, both as a financial drain, even before coming to the hospital, or because of the treatment, or by the time they have come to us they possibly have lost faith in the medical community. So we start from there.

Could you discuss some of the translational research your team is working on?

In a country like us there are two areas where the translational research should have a major impact. One is in the area of the screening because we all know that we are trying to tell that the HPV screening should be the primary modality of treatment. But then perhaps we have not sorted out what’s going to happen with all these HPV positive women. What you don’t want is a situation, with already the social taboo and everything that have, that you tell a woman, ‘You’ve got HPV positive.’ Now they shouldn’t be thinking it is HIV positive. So there are a lot of things and we know that it’s like the reproductive age, so many women are going to be HPV positive but not many of them are going to proceed to pre-cancer or cancer. Then if you start bringing all your HPV positive women to a colposcopy clinic I don’t think we are equipped or have even thought about it. So one of the major areas which we would need to concentrate on is itself at the liquid biopsy stage or even with the liquid specimen actually to determine which of those HPV positive, depending on what we are doing as DNA testing which is commonly done, that we could really predict the ones which do not need to go to a colposcopy straight on but maybe wait, or the ones which need to go straight on, or the ones which actually don’t need to go. So that is one of the areas with the sample size which we have. Also we have a different kind of microbiome, immunological background and everything so those have to also be put into the context in determining which are the HPV positive women who are going to persist. So that is one area which will have a huge amount of economic impact as well as a social, cultural and infrastructure impact on how you design your screening services at a tertiary care level.

The second area which is very important for us, because we will be contributing to a very large number of patients who will be presenting with radiation resistance, i.e. with this huge number of patients coming for treatment for 2b, 3b and 4. Then you start seeing that 25-30% of them are actually not going to respond to radiotherapy. So it does actually make a point that in our scenario we need to allocate resource for some research in picking up those patients who are at higher risk for failing. You might argue what you are going to do with them. If it’s a big 1b or a 2a and you know beforehand that they are not going to do well with radiation, just we think that we want to do targeted chemotherapy, maybe they are better off with having surgery before. Or if you know that they have some risk factors you can modulate your chemotherapy beforehand or even go for adjuvant chemotherapy which is something which we haven’t, sadly, thought about in our country. International trials are there but I think the patient milieu and the behaviour, the disease biology, maybe the stage of the disease, everything is different. In our scenario that is a huge need which maybe needs to be addressed.

We have a translational research unit inbuilt in our hospital here; we have a very good state of the art biobank. Funding is always limited in India but we are fortunate enough to have a government of India, big funding, looking into a system biology cluster approach where this sort of multidisciplinary involvement with clinicians and scientists from various disciplines can be integrated. We have been fortunate to get one of those grants and we hope to look forward to get some meaningful data research out of it.

The other thing which we lack is actually we do all these omics and all but we don’t have an infrastructure in India to bring it back to the clinic. So the clinic has gone to the bench, we have asked the questions, but from the bench to translate to the clinic we do not have phase I clinical unit trials. Phase III, yes, maybe we are trying to get part in international clinical trials but for all the new things, the drugs, the medicines, the plant extractor, whatever people are trying to invest, especially the government of India has got a huge interest in investing on extracts, biological extract. But we actually do not have the infrastructure how to test them on. So this is something, again, which I think is the need of the hour to build into the clinical research integrated programme.