New treatments for cancer

New chemical treatments that selectively target cancer cells and leave the healthy ones intact. 

Chris Smith spoke with Dr Neill Martin, Chief Operating Officer and Co-Founder of Mission Therapeutics. They're trying to trigger what they call "synthetic lethality" in cancer cells by deactivating certain critical systems that cancer cells rely on to grow and remain alive. Healthy tissues have backup systems, but cancers don't, so switching off these systems makes the cells self-destruct.

Chris -  Tell us first of all, what's going on in a cancer cell genetically.  Why does it have this Achilles' heel that you're plugging into?

Neill -  So, a cancer really likes to be genetically unstable.  It likes to be very mutational.  So, what it does is it tries to switch off a number of these genes which protect a normal cell.  By switching those genes off, it actually becomes mutational and therefore, it creates the sort of environment that cancer likes to grow in and force the sort of growth of that cell.

Chris -  So, what you're saying is that in order to be a nasty cancer, it's a sort of a self-fulfilling prophecy. If it turns off a lot of these genes that normally keep cells in check, it makes itself able to gain lots of other properties of a cancer, but at the same time, the downside is that it's more vulnerable.

Neill -  That's right, exactly that.  So for us at Mission, what we do is we study the DNA repair processes and within the DNA repair processes, a normal cell has about 5 or 6 of those.  A cancer cell will try and switch some of those off because it wants to actually increase its mutational rate.  DNA repair protects the DNA.  So, when it does this, it then actually creates that sort of environment.

Chris -  Isn't that roughly how current therapies against cancer work?  They're exploiting the fact that cancer cells are actually quite weak and they're very easy to damage.  And so, when we give these drugs or radio therapies and things, you're actually making more damage to the DNA which in turn makes the cell fall apart.

Neill -  That's it, correct.  But the big problem with that is it also damages the DNA of a normal cell and that's where you get the problems and that's why a lot of patients suffer from this sort of chemotherapies that are given.  What we're now trying to do is actually, use that Achilles' heel, understand it a bit more, and actually tailor the treatment to that cancer cell and rather than the normal cells and therefore, protect the normal cells but kill that cancer cell.

Chris -  You're going in and finding which of these systems have been disconnected in the cancer so that you can hit the one that it is the thread it's dangling by genetically.  But isn't by definition cancer a sort of mixed population?  If we go and look at a cancer, we'll see, because of all these mutations and genetic changes, we're going to see lots of cells that are screwed up in lots of different ways.  So, is there just one Achilles' heel?

Neill -  What we're finding I think is that for a number of cancers that there's a very early switch and therefore, that you do get heterogeneity in cancers and different types of genetics that are evolved from that, but there'll be a very early switch.  We're starting to see that for example, the DNA repair processes are one of those early switches that change the environment.  Therefore, all the tumour cells that then evolve from that tend to have that same genetic background.

Chris -  So, they're still inheriting that nonetheless.  So, if you go in on that, that is the one thing that is consistent and constant throughout all of the tumours.

Neill -  Yes, exactly.

Chris -  What would you do then?  Do you go and say, "Well let's have a sample of someone's tumour and let's unpick it genetically and see what these areas are that it's deactivated" or what it's still using, so you know how to go in?

Neill -  Yes, exactly.  So, the way that we will be evolving this is by creating the sort of genetic test to go with the therapy so that you can actually then diagnose or take a biopsy or as Ian was saying, some sort of biomarker even from the blood, get to understand what that tumour type is.  And then because we actually know that it might have this genetic defect, actually tailor the treatment to that cancer.  That's really the personalised healthcare that we're looking for now within the sort of cancer field.

Chris -  Well, let's look at how you do that then.  So, you look at a tumour, you find what its genetic mechanisms are and you say, "Right, we're going to target this particular mechanism."  How do you then go about that, making a treatment for a person to do that?

Neill -  Well, because we know that, what we can do is we can actually take that right back to the fundamentals, so almost back to the Petri dish within the lab.  So, we then can actually start to look at, "Okay, this is what's actually been switched off."  We can then look to see what's actually remaining within that cancer cell and then look for the drugs that switch those mechanisms that are remaining within the cancer cell.

Chris -  But do those drugs exist?  Are there chemicals already that you could put your cancer in a dish and ask, "I want to turn off that particular gene and there's a drug that'll do that"?

Neill -  We're actually starting to see within the sort of clinical trials, a number of those drugs which are actually personalised and actually targeting certain tumours and different tumours in a non-cytotoxic way.

Chris -  In other words, not killing other cells in the body.  So, they should be very, very discrete.  It should just go through the tumour because your other cells in the body have all their other systems intact even if you disable temporarily with your drug, one of them, the other 5 strands are going to keep it together.

Neill -  Exactly, that.  

Chris -  Where are you in terms of the progression towards a market with this?  Are you at a clinical trial stage yet?

Neill -  We are.  Previously, we've created a number of products which are now in clinical trial.  At Mission, we're still quite - our labour is still in the pre-clinical.  What they call a pre-clinical, the sort of testing phase.  And we're probably about 4 or 5 years away from clinic in terms of being able to try these products out.

Chris -  What sorts of diseases are you going for?

Neill -  Well there are a number of diseases, but we don't know now, that diseases such as what's known as BRCA of which there was a high profile case of Angelina Jolie recently. Those diseases really are genetic diseases, and if you can get the right treatments, for those types of diseases you can actually selectively kill the cells.

Chris -  She underwent a double mastectomy, didn't she, as a preventative measure. She didn't have breast cancer but she does have that gene which we know is linked strongly to premature development of breast cancer at a very young age. . are you saying that had she pursued your approach, given the option of course, I mean it wasn't a choice at that time, she would potentially have the option not to have a mastectomy but she could have what you're offering instead?

Neill -  That's correct, Chris. Where we would like to get to is to have the sort of toolkit of drugs where we can actually offer these patients an alternative to surgery. And I think that will come, I think it's just a matter of time, because once we actually design the right drugs, we can use them then in those sorts of settings. And that'll give the alternative and therefore they'll hopefully be able to just live off rather have the surgery, the drug. 

Chris -  Does she have to wait, in Angelina Jolie's case, until she gets breast cancer and then has your treatment, or could it be used preventatively in anticipation of getting the disease?

Neill -  For us, we would like to get the point where its use is preventative in a prophylactic setting where you could actually treat these patients prior to them getting any symptoms and what'll it do is any cancer cells that actually come through at an early stage. And it might be that you need to do this sort of 20's or 30's when the possibility of those sorts of tumours starting to grow. It would be a preventative measure.

Chris -  Neill Martin from Mission Therapeutics, thanks very much.