Colon cancer in a culture dish
Colon cancer accounts for more than ten per cent of all cancer cases in countries like the UK. And one important question that bowel cancer patients often face is whether or not to have chemotherapy: because while this is guaranteed to cause side effects, which are often unpleasant, there’s a chance that it might not affect the disease outcome at all. Which means you’d suffer the side effects for nothing. So, to find out who will - and more critically who definitely won’t - benefit from chemotherapy, researchers in the Netherlands have now developed a technique to grow a miniature version of a patient’s colon cancer in a culture dish so they can test out the chemo drugs before giving them to the patient. Chris Smith spoke to Emile Voest from the Netherlands Cancer Institute…
Emile - I'm treating patients with colorectal cancer with multiple lines of chemotherapy. And the frustrating part is that this chemotherapy will give you all types of side effects, but the chances that you are going to be successfully treated, in the sense that you tumour will shrink, is less than 50 percent. So I would like to have a test that identifies patients who will not benefit at all, so we can prevent those patients from undergoing the side effects of chemotherapy.
Chris - Because at the present time, one has to try before you buy if you like, isn't it? You have to try the therapy you find out the hard way if it's not going to work. And by then you've not only suffered all the side effects, you've potentially wasted time when you could have been on a more appropriate or more effective therapy.
Emile - Yes. So the chemotherapy for colorectal cancer is absolutely extending life. So you have four times longer to live with the chemotherapy then without chemotherapy. So people generally want to just try the chemotherapy. But the unfortunate part is that more than half of the patients will not have any benefit yet they will still suffer the side effects.
Chris - What's the alternative that you're proposing we might be able to do?
Emile - With the new technology that comes around, we're now able to grow from an individual patient the cancer, in a dish outside the body. And those little tumours outside the body in the dish are called organoids. And once we are able to do that, you're able to expose those organoids to the same type of treatment as you expose the patient to see which tumour cell was sensitive to a treatment and which one was not.
Chris - How do you make these mini tumours in dishes in the first place?
Emile - When the patient has a metastatic disease, they're either metastases in the liver or lymph nodes. You take a biopsy, and then you can grow with a specific cocktail of growth factors, you can grow those tumours in the dish. In our study about 60 percent of the times we succeeded in growing these organoids.
Chris - How do you know that the organoids you grow are genuinely representative of that person's disease?
Emile - That's work that we've done over the last couple of years and we have looked at that extensively. So we compared material from the tumour of the patient with the organoid, and I would say that the organoids preserve the same features that the tumour in the patient has.
Chris - And you treat these organoids, these tumours in dishes, with the same drugs that you're going to give the patient, but how do you, again, know that the way that drug behaves in the dish is going to recapitulate what's going to happen to that patient?
Emile - Yeah that's the key question. So for chemotherapy, usually you give chemotherapy as an infusion and you have like a peak level in the patient, and then in 24 hours it drops and it's cleared from the body. If you start exposing it in a petri dish you will have an exposure of a continuous amount of chemotherapy. So we kind of invested a lot of time to figure out what is the best way to have the chemotherapy combined with the tumours in the petri dish. And then secondly, because chemotherapy is usually given as a combination of chemotherapies, we also needed to come up with, that we have multiple chemotherapies in the same dish. We figured it out and we were able to, at least for one type of chemotherapy, very successful to identify the patients who did not respond to that chemotherapy.
Chris - And how do you think this is gonna make a difference clinically?
Emile - Yes. So there are two ways to approach this problem. So one is to see if you can use the test to identify patients who will respond. That is a fairly difficult question because responding can mean that it's remaining stable or that it shrinks. So there are a lot of grey areas. The tumours that would grow despite the chemotherapy, that means you would identify the patient who had absolutely no benefit. And as long as we do that with a high level of sensitivity and specificity, if we sit down with the patients we can tell them and say, you will not respond on this chemotherapy. So we need to find alternative choices.