Researchers probe molecular changes contributing to the evolution of nasopharyngeal carcinoma to seeks new ways for cancer treatment and deterrence

BY SYAMIL ZAHARI

In this multi-part series, AMOR Media sat down with Cancer Research Malaysiaai??i??s head of Nasopharyngeal Cancer Laboratory Dr Vyomesh Patel along with members of his research team to talk about the efforts in nasopharyngeal cancer research.

UK-expat Dr Patel was formerly a staff scientist at National Institute of Dental and Craniofacial Research at the National Institutes of Health in Bethesda, Maryland, USA, before journeying to Cancer Research Malaysia to lead a team of molecular biologists seeking improvements on the most basic understanding of the molecular mechanisms underlying the initiation and progression of nasopharyngeal cancer (NPC), and use of the emerging information to develop markers for the early detection of NPC and novel therapeutic approaches for prevention and treatment.

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Dr Vyomesh Patel: Cancer Research Malaysia works on cancers endemic to Malaysians; breast cancer and head and neck cancers, for example, are quite prevalent here.

For breast cancer, the work is carried out by our CEO [Prof Dr Teo Soo Hwang]. Research work on head and neck cancers, i.e. oral cancer and nasopharyngeal cancer, is carried out by myself. The other team we have, as well, is the Drug Discovery team.

My background is specifically in oral cancer, and so Iai??i??ve come here because of the opportunity to work with the [Cancer Research Malaysiaai??i??s] oral cancer team, and to try and develop the Nasopharyngeal Cancer Programme into something solid.

What we want to try and develop is something more benched to experimentally try and understand nasopharyngeal cancer ai??i?? from how it starts, and how it rapidly progresses to the point where it is quite fatal to patients.

The nasopharyngeal cancer itself ai??i?? if youai??i??re a Malaysian, young, male, and you are at the age group where you donai??i??t care about how much you smoke, how much you drink or you donai??i??t care about what you eat, and specifically if youai??i??re of Chinese origin ai??i?? you are much more likely to develop nasopharyngeal cancer.

So, in terms of research question and clinical question: How do you identify these individuals who are at risk? If you can identify anything from the body routine test or diagnostic test, then you follow up on them closely, either bimonthly or trimonthly, to see if there are symptoms of cancer development.

dr-vyomesh-patel-pullquoteThe clinical challenge is that this [nasopharyngeal] cancer develops in an insidious way. The symptoms could be very similar to having irritation in the throat or in the nasal cavity, and the doctor would say, ai???Oh, youai??i??ve only got cold, or ai???Youai??i??ve got an allergy.ai??i??

What we want to do is knowing quickly what is wrong, so that the patient could go for a check-up immediately. By going for a check-up, an ENT surgeon who will take only 10 minutes to look at a small area by putting a scope up the nose where nasopharyngeal cancer starts and see whether it is smooth or rough. If itai??i??s rough, then the ENT surgeon will know something is wrong and will keep an eye on it; or, if it is cancer, then the surgeon would be able take a small biopsy and have it tested.

So, our goal is to help these people who are at risk and try and detect the cancer early. With any cancer, the best cure is prevention.

Altered genetics

We also try to find the biomarkers ai??i?? whether itai??i??s in the blood or in the saliva or anything, to specifically see if the cancer develops ai??i?? i.e., markers in the genetic material of the cancer that will help us understand what leads to its development.

dr-vyomesh-patel-2These are the altered genetics. It basically means that the genes became abnormal or altered to a point where you get abnormal function that in turn became a disease, a pathological disease. So what we are trying to do is design model systems to better understand it and use the new technologies currently available. This is called the next-gen sequencing that will sequence the DNA of the cancer sample to read what is altered.

Once we find those, then we can start thinking about how we can help cancer patients, not necessarily to be cured, but treat the cancer as something containable instead of a life sentence. Itai??i??s very similar to type 1 diabetes. Think of how many people around the world who have type 1 diabetes ai??i?? itai??i??s quite a large number. They are at risk only if they donai??i??t contain that disease. Itai??i??s the same with nasopharyngeal cancer.

Technology now has advanced so much. Itai??i??s very affordable to have the cancer genome sequence and to find out what causal genes are. With the causal genes, we can find out pathways theyai??i??re involved in and whether those are druggable. This is now ongoing programme here, not only for the NPC but also for the oral team.

One of the emerging top trends to look for targets, as Iai??i??ve just alluded to, is called a CRISPR/Cas technology which is basically associated with gene editing. We can use the genome-wide CRISPR library and look for functional loss, and look for additional druggable targets that we may be able to think of, to perhaps develop new drugs. We could identify a good target, and look at its crystal structure ai??i?? if that target is already known in the scientific literature, for instance ai??i?? and get a crystallographer to help with the crystal modelling and so forth, and see if there are libraries of small molecules that might be able to interfere with it.

It comes down to how we can do it technically in the lab, as well as learning new ways. We need to teach the young generation as well, not only the old methods from hundreds of years ago, but the new methods which will be more efficient in giving quick answers or clues.

Model systems

My background [at US National Institutes of Health] has told me that if the model systems ai??i?? which we are trying to set up here in Malaysia ai??i?? if it showed that something was altered and that itai??i??s a good target, then we could search the library for currently available data to find one that is very specific for this target in the pathway. We may find that at the upstream of the target, things were altered. We could then find the most downstream target that we can aim, and see if we can switch off all above it and get the desired effect.

dr-vyomesh-patel-3So we did that, we actually took it from lab-based into a clinical setting. But this was back in the United States. We want to try and recapitulate that here.

Iai??i??ve mentioned about making model systems. We canai??i??t do research or look for cure if we donai??i??t have model systems for nasopharyngeal cancer. There is still a big gap between where we are and what we ultimately are going to do.

This is what we want to achieve here. What Iai??i??ve mentioned is the big picture ai??i?? the clinical questions, early detection, cures and so forth. Itai??i??s a way to find cancer cure, to treat cancer patients, and to give them a better quality of life once they have actually survived.