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Asked by anon-332080 on 28 Jun 2022.
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Tammy Piper answered on 28 Jun 2022:
Tumour heterogeneity arises when tumour cells within the same population start to collect different genetic mutations to each other, during their broken cell cycle growth. This can cause issues when allocating patient treatment as if drug A only works on a patient with a tumour that has a lot of tumour protein B, and when looking at the tumour some of the cells express high levels of protein B but some have no protein B – what treatment do you give the patient? Will drug A be as effective on tumours where only half the tumour cells express protein B?
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Sophie Richardson answered on 28 Jun 2022:
There are two types of heterogeneity that can occur in one patient – INTRAtumour heterogeneity (in a single tumour) and INTERtumour heterogeneity (between tumours in the body). Intertumour heterogeneity can occur when someone’s cancer metastasises (moves and makes another tumour in the body). In this case, heteogeneity can occur as the cells need to adapt to the new environment (like an animal adapting from a hot to cold environment, for example).
Intratumour heterogeneity can occur because of treatment. A good example of this is BRAF inhibitors, which are used when a melanoma patient has a specific mutation in the BRAF gene. Melanoma with the BRAF mutation respond really well to treatment. However, there are other mutations that can happen that cause the cancer cells to become resistant to BRAF inhibitors. If we give the patient lots of BRAF inhibitors, the cells with the mutations that cause resistance survive while the others tend to die. This causes heterogeneity in the tumour, as we have cells with different genetic mutations.
Ultimately, heterogeneity is caused by evolution of the cancer. The cancer wants to get better at dividing faster and surviving in the body, so cells evolve to do this in different ways. If you’re really interested in this, I would recommend searching the term ‘clonal evolution’ on the web. There is some really cool research going on in this area!
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Karin Purshouse answered on 28 Jun 2022:
Sophie and Tammy have given excellent answers – I’d only add that tumour heterogeneity probably emerges from the beginning of a cancer’s development, even when it’s only a few cells in size, although this heterogeneity probably isn’t very significant at the beginning – but as time goes on, the cells become more and more different with every division – and as the others have said, treatment and resistance to treatment creates even more heterogeneity.
It’s a real challenge for the reasons Tammy outlines. We generally only do one biopsy – what are the chances this sample is representative of the cancer as a whole? What about the bits far away from the original cancer (metastases)? Luckily there are cancer teams researching all of these questions!
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