New drugs on the horizon for pancreatic cancer

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Published: 5 Jul 2017
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Dr Philip Philip - Karmanos Cancer Center‎, Detroit, USA

Dr Philip talks with ecancer at ESMO GI 2017 about new drugs that are on the horizon for pancreatic cancer and his views on development. He discusses ongoing clinical trials and what he believes may be the outcomes of those trials. 

Dr Philip goes on to talk about the need to target the microenvironment and stromal cells of a tumour and the DNA repair pathways. 

The title was New Drugs on the Horizon with respect to pancreatic cancer and what I was thinking of the future in terms of the development. My talk focussed mainly on what is really coming up in the next few years based on what we have learned from all the years in the past and based on what is currently ongoing in terms of clinical trials.

I focussed on several areas which are of interest; one of them was targeting the microenvironment, the stroma. There’s a drug which is pegylated, PEGPH20, which is currently in clinical trials and it has shown promise in a select group of patients whose tumours overexpress a protein called hyaluronan, we call it HA. That’s now in phase III trials.

I also discussed targeting DNA repair pathways that are deranged and abnormal in pancreatic cancer cells and using them as an opportunity to use drugs such as platinum compounds or even PARP inhibitors. I also discussed other more novel areas of work involving targeting tumour metabolism and also using drugs that target a protein called mesothelin and there are a number of approaches trying to use that protein as a target with antibodies or even CAR T-cells to try to attack the pancreatic cancer cells.

Basically my thought was we learned a lot and now we’re moving into new drugs, new approaches, new strategies and ultimately, in my opinion, it will be putting everything together, getting enough data to generate molecular classifiers of the disease that will help us to really decide what to give to each patient, make it more personalised.

We’re developing treatment tools now where what we’re lacking are how do we really apply those treatment tools that we have in treating patients so that we can get the maximum benefit. In my opinion it will be combination treatments. But we can’t just do combinations empirically it has to be biologically driven, it has to be rationalised, it has to be personalised because that’s the best way we can not only save toxicity on patients but also don’t do futile treatment that costs a lot but benefits very little. So that’s really very important.

Just to give you an example, one thing which I discussed also was targeting the stem cells in pancreatic cancer. There is some preliminary data that a drug that targets STAT3 in the cancer stem cells called napabucasin, when combined with chemotherapy, with gemcitabine and paclitaxel, can be producing interesting results. At the end of the day one would be able maybe to put combinations together, it could be stem cell targeting plus metabolism targeting, it could be stem cell targeting plus DNA repair, but we have to go about figuring out how we can really do these combinations and which combinations really fit a given patient very well. It is a situation where we’re moving into big data because there is no simple data in this disease unlike some cancers where there is one driver mutation that you can use one drug and get a very good benefit, just to give you an example like patients with gastrointestinal stromal tumours, they have c-KIT mutations, you use one drug and you can keep the patient on that single drug for a long time in a very good condition and patients in remission. That will not happen in pancreatic cancer based on what we know about it. What will happen is that we have to bring in drugs together.

Something else which I talked about in my presentation was immunotherapy. That has really revolutionised how we treat some cancers. In pancreatic cancer we describe the cancer itself as being an immune desert, desert with a real sense of the word because there are very few effective T-lymphocytes that can kill the cancer cell. But also there are a lot of cells there and other cytokines that produce an immune suppressive environment. For that reason we cannot simply give patients what we give, for example, in melanoma or non-small cell lung cancer like PD1 or PD-L1 inhibitors and expect to benefit. Vaccines didn’t work either. So now there are a lot of combinations that people are testing which may work to regenerate the T-cell function and also try to remove the suppression of the immunity to be effective.

In my opinion the next five years will be very exciting but at the same time the next five years will require a lot of hard work, a lot of intense work. The most important thing is people cooperating together to do this. As I said before, we’re generating a lot of data and that data has to be put into some form of an actionable way.