How come drugs like tamoxifen works at high doses because it shuts down tumor growth, but at lower doses it can turn up tumor growth?
In: Biology
Cancer is extremely complicated. There are like, 20 different things that have to go wrong for a tumour to grow and each of those things is mediated by multiple extremely complicated interactions. This is why finding a cure for any kind of cancer is so hard – the same kind of cancer can be caused by multiple different things.
It’s worth noting that documentaries can make mistakes (and can even contradict themselves), and I can’t find anything online that suggests the dose of tamoxifen is responsible for stopping or promoting tumour growth. In fact, what I can find suggests that low doses of tamoxifen also has a tumour suppressing effect.
Theoretically speaking, however:
Oestrogen is a growth hormone – it tells cells to make more of themselves. Cancer is basically a malfunctioning form of cells making more of themselves, a form that is out of control. The reason these systems go out of control in the first place is because mutations arise in the genes that regulate cell replication. A cell is most vulnerable to mutation while it’s dividing. Since growth hormones tell cells to divide, high amounts of growth hormone means high amounts of cell division, which increases the chance of any given cell developing a cancerous mutation.
Oestrogen is detected by cells in the first place because of proteins on the surface of the cell called receptors. These bind to the oestrogen, and when that happens, they change shape. This change in shape recruits a bunch of other proteins which go on to tell the cell to replicate. Tamoxifen has a similar shape to Oestrogen, which means that it also binds to some oestrogen receptors. When it does, however, the receptor *doesn’t* change shape, and so it doesn’t trigger cell division, but it *does* block the receptor so that actual oestrogen can’t bind. Tamoxifen therefore essentially prevents oestrogen from telling certain cells to divide. And if cells aren’t dividing, it’s very hard for them to become cancerous.
However, not all oestrogen receptors are the same. Tamoxifen can block oestrogen receptors in the breast, but oestrogen receptors in the uterus behave differently (according to what I googled) – Tamoxifen looks the same as oestrogen to them, and doesn’t have an inhibitory effect. So, essentially, for the uterus, tamoxifen is just extra oestrogen which means it also helps promote cell division.
Also, since cancer cells by their very nature are mutations, and can develop mutations more easily, it’s possible for the genes that code those oestrogen receptors to gain mutations too. Those mutations can be one that make the cell no longer require the signal of oestrogen to divide, meaning tamoxifen would have no effect on them, or could even be mutations which mean they respond to tamoxifen in a positive way instead of a negative way.
Can you provide a source? I haven’t been able to find anything that says tamoxifen increases tumor burden at lower doses.
Latest Answers