The discovery of a novel cancer inhibitor

The discovery of a novel cancer inhibitor

Arun M Dharmarajan, Associate Dean, South Asia Research Initiatives and Winthrop Professor, School of Anatomy & Human Biology has been researching the Ang001 inhibitor for the last four years. His research has finally yielded results and will be soon used for the treatment of ovarian cancer. He speaks about the development of the protein and scenario of the oncology drug market in India and Australia, with Arshiya Khan

Tell us about the protein that you have discovered?

We discovered the protein (Ang001), which is secreted and synthesised by almost all the cells in the body. As cancer tumours are very smart, they put out signals (ie. the growth signals) and attract blood supply because they need oxygen for growing. Ang001 cuts the blood supply to the tumour, so that the tumour cannot grow.

What is the progress on the protein in terms of animal studies?

We developed human tumours (eg ovarian cancer) in the mice and then injected Ang001 in them. We used immune deficient mice and looked at the tumour growth. It was surprising to see that there was no tumour growth at all after we treated them with Ang001.

How challenging is it to treat cancer over other ailments?

Cancer is something in which prevention is a problem. Most of it just happens because of mutations. Mainly it’s hereditary but even environmental factors are a cause. So it’s basically a treatment. What we are trying to do is prolong the life span of cancer patients.

The tumour cell is not a disease, because most of the times when cancer patients are diagnosed of the cause they are at a late stage. Even though there is education and awareness on the said subject, still people don’t go for regular check ups and, as a result, when breast, ovarian or prostate cancer are diagnosed it is too late and there is a very little chances of survival. So if this protein progresses successfully it will prolong the life span and give good quality of life to all these patients.

How will Ang001 be different from the available medications to treat cancer?

The drug that is currently being used to treat cancer is Avastin, which is very expensive. It is an antibody and it blocks the receptors of the growth factor. However, Ang001 will not have any side effects as it is being created in the body.

We tested this on the mice. We had six mice in each group. Even after injecting the mice with the protein it did not have any side effects on the heart, liver or lungs. So there is very little toxicity. On these kinds of studies there is a lot more research to be done and for the toxicity studies, we have got the complete dose.

The other thing that we have to do is to find out how long these proteins will stay in the bloodstream. We kept these mice for 40 days and then because of ethics and regulatory requirements, we had to sacrifice these animals. But we don’t know if we kept these animals, there would have been a recurrence of the disease, so we are waiting for that.

The cancer drugs that are available are very widely used irrespective of where the patients are from. Unlike other diseases the whole idea of treating cancer is that you have to cut off the blood supply and then kill those tumour cells. This is what chemotherapy agents or anti-tumour cells do. But now there is a big push for combination therapy. That is anti-tumour drugs and anti-angiogenic drugs (which cuts off the blood supply), and also the combination of these two; which we think will totally suppress tumour growth.

There are one or two drugs in the market already. There is one drug that is used only for treating colorectal cancer, which has recently been approved to treat breast cancer. So there is no drug till now that will help in the treatment of all types of cancer.

Will Ang001 be applicable to treat all types of cancer?

One cancer treatment may or may not take care of all the types of cancer. We have tried this only on a very aggressive form of ovarian cancer, which normally does not respond to chemotherapy treatment and had good success.

Does Ang001 also have any other implications?

We are hopeful that Ang001 may also be used for the treatment of other diseases related to excessive blood vessel growth such as diabetic retinopathy and rheumatoid arthritis.

Because this is an anti-angiogenic drug it will have multiple implications, cancer is just one thing. It has got implications in arthritis and any hyperproliferative diseases like skin diseases (in which there is an increase in the blood supply).

How will you take this protein ahead in terms of drug development?

It’s not given orally but we should be able to inject it through IV and target the specific tumour. That is going to be our next strategy. After we finish with our animal studies we will do Phase I clinical trials.

Have you filed for any patents to the FDA?

Not yet. First we have to complete the toxicity studies with animals. And then we will go on to the Phase I clinical trials. We have not yet started the Phase I clinical trials but it will be very small in numbers, like five. These will be done on cancer patients from Australia. However we got the patent for this protein in October 2007. We had the Patent Corporation Treaty (PCT) approved then we applied for it in each country, so we are very well covered as far as the IPR is concerned. We will be launching the drug globally in India, Japan, US and Europe.

Who funded this research?

The project was supported by the NHMRC (Australia), Raine Foundation, Cancer Council W.A., Office of Industry and Innovation at The University of Western Australia. We received a total grant of approximately $ 500,000.

What is the status of cancer research in Australia as compared to India?

There is a lot more funding in Australia. There is funding from the Cancer Council of Western Australia and Australian Post. Also there are various funding sources such as the National Health Medical Research Council and Australian Research Council.

There is a lot of research being conducted in India at various institutes such as AIIMS and Tata Memorial Cancer Institute, Mumbai. The treatments available are similar to other parts of the world with no one therapeutic agent being successful in all cases.

The market for cancer drugs is enormous and it is hard to predict when a successful treatment will be developed because cancer is a complex mechanism.

Not many Indian companies are doing cancer research in India, what according to you is the reason?

What is important is the affordability. The drug shouldn’t be expensive. The available drugs are only for rich people. Because this protein is internally produced and we will be able to synthesise more at a lower cost, the sale will also be at a lower cost; definitely not the same price as that of the drugs we have today.

With the kind of results that you have got with this protein, what are your plans for presenting the papers to medical journals?

Our study is being reviewed by the American Journal of Pathology. It will help in two ways, firstly we are the first one to show the anti-angiogenic effect for this protein and secondly, it will be good for pharma companies as it will show them that we have some feasible data.

Which Indian institutes and hospitals have you visited and are already in talks with? Will you be tying up with cancer institutes, hospitals, pharma companies in India?

I am talking to various institutes for the same. Within the next 12 months we will hope to finalise something. At present I am not in talks with any Indian company. Most of the companies that I am speaking to are American. The reason being I don’t know too much about Indian pharma. There are quite a few Indian companies that I know of but I am not sure how much work they are doing in oncology.

What is the expected timeline for the launch of the drug?

We are doing this research in collaboration with AU-KBC Research Institute, Anna University in Chennai with Dr Suvro Chatterjee, a research scientist.

As Phase I trial is expensive we will first establish partnership with companies and then take it forward.

The other way of doing it is; we can sell the protein to them outright and have the license so that they can fund us. There are few companies in Switzerland and US that we have approached. If they fund the research they get the priority.

What are your future plans?

Our plan is to establish strong partnership with industry to further develop ANG001 as a novel therapeutic drug for cancer treatment.