Browsing the BBC website today I found news about an article at the Journal of clinical oncology that presents research with the potential to help men with end-stage prostate cancer.
The article describes the Phase I clinical trial of a drug called Abiraterone acetate that so far seems to be quite efficacious (70-80% of patients reporting an improvement). The idea of the treatment is that prostate tumours rely on sex hormones (like testosterone) and that reducing or eliminating the production of some of these hormones will block tumour progression. As opposed to other treatments, the one tested by Dr. de Bono and his group and collaborators at London’s Institute of Cancer Research, blocks hormone production not only from healthy cells but also from the tumour cells themselves which might step in and produce what they need in order to keep growing.
The news can be found in English BBC and in Spanish El Pais although if you read the Spanish version you may get the idea that the entire work was carried out single-handed by Dr. de Bono, the leader of the project.
I know very little about human physiology, but are there not side effects to systemically blocking testosterone production? Or is this less of a concern since the patients advanced and are in dire need of some sort of intervention? Or is this a course of chemotherapy that is finite in duration?
Hi David, I have watched that even on Czech TV… In my view, the positive results of Phase I clinical trial are not worth of such, let me say, propaganda. My question is: cui bono? – Was that a message for investors?
Anna, blocking testosterone production (by either GnRH agonists or antiandrogens) is common practice in advanced prostate cancer. It is an effective treatment, but has many unpleasant side effects (including loss of lipido, erectile dysfunction, hot flashes, bone loss). But there is an urgent need to improve the treatement for those patients where antihormonal therapy no longer works. Chemotherapy has much more side effects and there are only a small number of effective drugs (most notably docetaxel).
Isn’t it true that the majority (if not all) prostate cancer patients progress from responding to testosterone-blocking treatment to being refractory within a small number of years? It’s the androgen-independent metastases that kill you, quite horribly.
The question becomes then, do these tumours become everything-independent after a few years, or are they really susceptible to losing contact with all hormones (and if so, is life, actually, worth living)?
I listened to an interview about this on the Today program yesterday (BBC Radio 4); and the researcher was claiming that the drug was to be used for prostate tumours that had not responded to other treatments… While I had already started cringing thinking that some drug was going to be hyped up after promising initial trials, the interview was actually quite conservative.
Reading the abstract, the term “castration-resistant prostate cancer (CRPC)” is rather more brutal than the language used on the radio…
Anna, that is a good point you made, one would wonder that all these hormones are produced for a reason and not just to favour prostate cancer. Thanks then to Martin for reminding me that when you have a developed prostate cancer and your prognosis is bleak then there is little room to be picky about side effects.
Richard, you raise a good point and I was thinking about the possibility myself. From an evolutionary perspective one would think that given some constraint in tumour progression (hormone production) some tumour cells might be able to develop alternatives to go around the limitation. Interestingly the trials have been going on for 2.5 years which means that long term results are still not known.
Hi Boris and Bronwen. It seems that this news has been very much in any news outlet in the last few hours. Still if they deliver only a fraction of what people expect (ans as Bronwen mentions, the author’s themselves are rather cautious) then there are reasons to be excited. Of course even if it works as it promises there are some caveats pointed out by other people in this forum.
There are many promising anticancer agents in Phase2 or Phase3 or even FDA-accepted (e.g. Velcade) although I never have heard such propaganda about them (on the other hand, I often hear such news about agents that are just ahead clinical trials).
“Richard, you raise a good point and I was thinking about the possibility myself. From an evolutionary perspective one would think that given some constraint in tumour progression (hormone production) some tumour cells might be able to develop alternatives to go around the limitation.”
I am going to insert a general comment now, because I am a bit lost. How can there be evolution of cancer? Cancer isn’t transmitted to the germline, cancer doesn’t go beyond the one inflicted individual.
Aren’t we merely talking about the physiological properties of the cell if we focus on limitations of the cell regarding their response to different levels of hormone production?
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I just went back to the very first blog entry of this blog on nature networks, and I have seen your analogy of treating cancer cells as evolving. But is there really a true comparison possible?
For starters, all cancer cells eventually undergo a massive extinction event when the local ecosystem (the organism) perishes. There will be no “tree of life” or even the more modern but still incorrect “bush of life”.
Secondly, cancer cells mutate. But so do all other cells in the body. Are they evolving as well? Not in my eyes, because it was already decided at a very early stage in the development of the organism that they will be all evolutionary dead-ends. Only the germline will produce a few lucky cells that actually continue the chain of life.
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I can see the value of the idea though. Maybe I need a bit more time to get used to it. That has happened before. Maybe the problem is that we got used to an evolving system of life that managed to stay afloat for a billion years and more, so the accepted doctrine prevents me currently from appreciating the application of the theory of evolution to short-lived evolving systems.
Do I get points for demolishing my own critique?
The introduction of the concept of an “evolving” tumor cell(s) certainly does complicate the discussion. Mark – as a former cancer researcher I can say that it is helpful to frame the changes in tumor cells as an evolutionary practice. One can then more easily understand how the tumor becomes such a heterogenious mass (there are numerous microenvironments within each tumor and this requires that cells have preferential pathways activated to continue to live). Absent the concept that the body is going to die – cells are likely not “aware” of the host they are part of – cells are just looking for self-preservation and passing on their genetic material to their offspring. So, it is lucky for us that these changes are not to the germ-line (a more robust discussion of the understanding of genetically inhereted cancer susceptabilities is an entirely different thread).
The response of cancers to therapies, be they anti-hormonal treatment, chemo, radiation etc. is to try and survive. Survival may then be what drives the metastatic event (matastasis being what usually kills people and not the tumor itself). So watching how quickly tumors respond to a therapy is just as important as if a tumor responds and ultimately what the trials need to show is that long-term survival or progression-free survival is significantly increased in a larger population (phase II and phase III). For now I will remain cautiously optimistic.
Hi Boris, unfortunately with these things only time can tell whether all these expectations are justified or not.
Mark, welcome to the blog. You definitely can take credit for arguing in favour and against your critique!
My view is that there is definitely evolution going on in cancer. This is not just my point of view and many people recognise two sources of evolution within our bodies: the immune system and cancer.If you find this perspective interesting, the seminal paper you might be interesting is The clonal evolution of tumor cell populations by PC Nowell. More recently there is work from Crespi and Summers and Maley and coworkers whose worked I discussed in old posts before I moved my blog to NN.
In brief, the evolution in a tumour covers a span of time that is significantly shorter than that in traditional ecosystems but the ingredients of variability (different tumour cell phenotypes) that can be inherited and differential fitness (where some phenotypes are more likely to survive and/or produce more successful offspring) are there. True that once the host is killed so are the evolving populations but that would be the case in any overexploited ecosystem (some bigger ones come to mind),
Mark, further to my comment yesterday I found that there is a rather recent and nice wikipedia entry on the topic of somatic evolution in cancer.
Moreover… from yesterday´s Nature:
Cancer-related inflammation p436
Alberto Mantovani, Paola Allavena, Antonio Sica & Frances Balkwill
doi:10.1038/nature07205