This post is going to be about combination therapies. Why are they needed? And how are they used?
Whenever someone is diagnosed with cancer, the clinicians will think carefully about what treatment, or treatments, to use. If the tumour is early-stage, then fairly straightforward treatments can be used – maybe surgery, or a course of either radiotherapy or chemotherapy. But, if the tumour is more advanced, or is inaccessible, then the medical team might decide on using two or more different types of treatment together. And one of the reasons behind this, is down to the make-up of the tumours themselves.
If you go by media reporting, you would think cancer is a single thing, with a single cause. But, as I’ve mentioned before, this is overly simplistic. The word “cancer” is an umbrella term which describes a wide range of different diseases which induce similar symptoms – uncontrolled cell growth. So, you shouldn’t think of cancer as a single disease, with a single cause, requiring a single cure.
And it is also overly-simplistic to subdivide “cancer” into separate diseases, each of which has a single, initial cause. As I mentioned back in The One And Only, cancer is a complex, multifactorial condition which does not have a single cause, but instead arises from lots of different mistakes, errors and damaging factors – some genetic, some environmental. That is what has started the movement towards Personalised Medicine. The idea that there is going to be ONE approach that will work as a one-size-fits-all cancer treatment against every tumour is wrong-headed.
But actually, the situation is even worse than that, because even within a single tumour, not all of the individual cancer cells are the same. As the tumour grows, different parts of it will start to behave differently. This could be because some regions of the tumour are nearer the blood vessels and so have better access to oxygen and nutrients.
Or, as cancer is caused in the first place by changes inside the cells, further changes can occur in some cells that alters their characteristics, while different changes happen in other tumour cells, so they start to behave differently. But, whichever way it happens, the upshot is that you end up with lots of cells behaving in different ways, even within an individual tumour.
Now, if you bear that in mind, it should be obvious why using a single type of treatment might not be a good idea. Every drug is developed to hit a specific cancer-related target. But, if different cancer cells inside the tumour change in different ways as the tumour grows, then you might find that one of these changes is to the target you are trying to hit. So, the treatment won’t kill those cells anymore.
This is why single treatments can fail. It’s not that the treatments themselves don’t work, is that they don’t always work. Therefore:
Targeting specific gene mutations is a valid approach, but it cannot be the ONLY approach, because not every cancer cell carries the specific mutation, therefore targeting it exclusively will not work in all cases.
Targeting an aberrant signalling pathway is a valid approach, but it cannot be the ONLY approach, because not every cancer cell displays errors in this signalling cascade, therefore targeting it exclusively will not work in all cases.
Targeting aberrant production of a specific growth factor is a valid approach, but it cannot be the ONLY approach, because not every cancer cell exhibits deregulation of this particular growth factor, therefore targeting it exclusively will not work in all cases.
Targeting aberrant metabolic regulation is a valid approach, but it cannot be the ONLY approach, because not every cancer cell exhibits aberrant metabolism, therefore targeting it exclusively will not work in all cases.
So that is why, in a lot of cases, a combination of different treatments is used. The tumour contains different populations of cells which behave in different ways. But, while one of these subpopulations might be resistant to one type of treatment, it might still be susceptible to a second. Another subpopulation might be resistant to both treatments, but susceptible to a third. And so on…
So, by using 2-way, 3-way combinations, you hope to hit lots of cancer-specific targets at once and get a double- or triple-whammy that kills all of the different tumour cell subpopulation sat once.
So, that’s the theory. Now, obviously, it doesn’t always work. Partly, this is because there’s a limit to how much treatment a patient can handle. Individual chemotherapy treatments can have pretty severe side effects, so if you are giving 2 or 3 of them, you obviously multiple these side effects – and there’s only so much the patient can take.
But another reason these treatments can fail is in the way that tumour cells respond to them.
….And I’ll talk about this in my next post.
Komarova, N., & Boland, C. (2013). Cancer: Calculated treatment Nature, 499 (7458), 291-292 DOI: 10.1038/499291a