Hello

[PaulW]

Hi All,

I’m the brother of another member of this forum, KarenW. As Karen has previously posted, our family has LFS. I also have cancer – Leiomyosarcoma (LMS for short). I was diagnosed with LMS last year, it was this that prompted Karen and I to get LFS tests done. I write a blog on my experiences with LMS (http://alotbs.blogspot.co.uk/) so I don’t need to go into that here.

I think this site and forum is a great initiative. LMS is quite rare but LFS is a whole lot rarer still and I think it is essential that people with the condition work together to support one another and to raise awareness amongst the medical profession.

One aspect of LFS that I am particularly interested in is how having LFS may reduce (or perhaps even increase) the effectiveness of some cancer treatments such a radiotherapy and some forms of chemotherapy. It is difficult to find information on this subject but it is something that is of great importance to anyone with LFS who is then diagnosed with cancer. I think this site could be a good place to share some information on this topic, what do others think?

Thanks,
Paul.

[PanP]

Hi Paul,

Welcome to the forum. I’ll take a look at your blog, but in the meantime I think I can at least point to some answers about LFS and responses to cancer treatments…

Cancer treatments that directly target tumours – like a lot of chemotherapy drugs, radiotherapy, photodynamic therapy etc – can kill tumour cells via different mechanisms. Some treatments kills cancer cells via necrosis – the cells are killed instantly – others damage the cells in different ways which trigger a form of cell death called apoptosis. With necrosis the cell is killed instantly and unavoidably, the cells burst or implode. With apoptosis a controlled process of cell death is kicked off and p53 is central to it. Without p53 the process that leads to cell death doesn’t complete and the cancer cell survives.

As I understand it, normally people with LFS produce enough p53 to make sure that apoptosis can happen. But within a tumour the TP53 gene may be further damaged so that no p53 is produced, or else the p53 that is produced is mutated in some way and doesn’t function properly. If this happens then treatments which primarily depend on apoptosis to kill tumours may not function as well as expected.

Newer treatments exist which don’t depend on apoptosis but either block growth pathways, exploit necrosis or engage other mechanisms to control tumour growth. In theory these kinds of treatments should act the same whether you’ve got a functioning TP53 gene or not.

I hope that makes sense…

[PaulW]

Hi Pan,

Many thanks for your response which makes perfect sense, in fact it matches my understanding of the situation regarding TP53 mutations and their interactions with specific cancer treatments.

It seems to me that it could be useful for those with LFS to collate a list of scientific papers that provide information on the interaction between specific cancer treatments and TP53 status in tumours. The paper you sent me via my blog is a good example of this type of information, another one is this study that I found that looks at the efficacy of different treatments for TP53 mutated breast cancer (I feel that this paper also does a very good job of illustrating the subtelty of the topic):

http://www.ncbi.nlm.nih.gov/pubmed/18544968

I know there many complications and caveats here, but it seems to me that people with LFS are likely to have a higher percentage of tumours with TP53 mutations than the broader population and that as a result, even in the absence of any specific sequencing of tumour genes, it could be interesting for LFS sufferers to be aware of what the research says about how the efficacy of a specific type of treatment may be impacted where tumour TP53 is mutated.

This topic does not seem to be something that my oncologist has a handle on and I’m sure he is not alone in this; well informed patients may be able to stimulate some additional research and consideration on this issue from their oncologists and this could result in more well informed treatment decisions.

I would be happy to provide links to the papers that I find on this topic and these could then perhaps be made available from this site?

Best Regards,
Paul.

[PanP]

Paul, thanks for the pointer to the breast cancer paper, it looks interesting.

While I like the idea of drawing up a list of papers or a database on what treatments are impacted (or not), by p53, the reality is that things are far more complicated than they seem (which is complicated enough as it is). For example, I always assumed that LFS patients would have tumours that were lacking p53 completely, but according to my interview with Galina Selivanova ([url=http://http://www.tp53.co.uk/index.php/interview-with-galina-selivanova]http://www.tp53.co.uk/index.php/interview-with-galina-selivanova[/url]) this isn’t the case. Mutated p53 can provide a survival advantage to tumour cells, so LFS patients, like all cancer patients, might have tumours swimming with mutated p53 rather than no p53 whatsoever. All this makes working out which drugs or treatments are more or less likely to work with LFS patients incredibly complicated.

Further down the line I think we’ll come to the point where there are drugs like PRIMA-1 which will convert mutant p53 into ‘proper’ p53, and that these combined with standard treatments will make a huge difference.

In the meantime, I see from your blog that you’ve decided to cut down on oily fish as that’s a potential problem with some drugs. Do you have a reference for that? I’d like to follow up because most work that I’ve seen says the opposite – omega-3s are essential…

PS – Feel free to drop me an email (anticancer.org.uk at gmail.com) if you want to talk about stuff but not on the forum.

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