What causes PCa cells to mutate?

[mandrake248]

Hormone resistance (as well as resistance to antiandrogens such as Xtandi and Zytiga) occurs because prostate cancer cells mutate. For some, hormone resistance develops in only a short time (months to a year), for others, it occurs after a much longer time or never(?).

Has research been done to determine what factors affect PCa cell mutation? (genetic factors, Gleason score, doubling time, environmental factors, etc.). One hopes that there might be controllable factors that can inhibit prostate cancer cell mutation (pharmaceuticals, diet, herbal supplements, intermittent fasting, etc.).

[Gemlin_]

Cancer cells mutate all the time at high rate. If a mutation is beneficial, such as "growing despite of low testosterone level", then that mutated (castration resistant) cell type will take over from the original (castration sensitive) cell types. It's mother natures Natural Selection principle! Bad luck if it happens early and luck if it happens late.

[Tall_Allen]

That's what cancer is. The brakes come off and the cells mutate. There are a number of DNA-repair proteins that are no longer expressed or that are only expressed in mutated, non-effectual forms. Yes, a lot of research has been done on them. PARP inhibitors are one class of medicines that work when BRCA is mutated.

[LearnAll]

The change from androgen sensitive to Androgen resistance occurs in different men at different time span, It is true some men either do not convert to hormone resistance or convert after very long time.Some factors for this conversion are (1) genetics (2) degree of undifferentiation (Gleason), Type of diet (plant based delay it), General good health and regular physical exercise .

In general, high PSA type convert later than low PSA type with aggressive variants,

Excessive and strong continuous suppression of androgens motivates cancer cells to mutate and use other pathways to grow....intermittent suppression of Androgens delays conversion.

One clue about how long the Androgen sensitivity is likely to last..is Nadir PSA (lowest PSA after ADT) and Nadir T (lowest level of T achieved after ADT.

[Poowater]

Only rely on scientific evidence proven in studies. Give anecdotal evidence a miss.

[kaptank]

Very complex issue. Many of the changes to castrate resistance are not necessarily genetic but biochemical changes in the cell to changes in environments (like low T) - dormant pathways activated. This is a very adaptable critter. Over time, yes there are mutations.

[spw1]

I have been thinking about the concept of hormone resistance lately. Despite a very good regime of clean diet, exercise, de-stressing and ADT, my husband's PSA started to creep up in May this year. His ADT worked effectively for less than a year before PSA started to rise.

I asked the MO to measure DHT, not just T. They do not normally do this in Canada so we paid to test it privately. I read that Dr Myres liked to keep the DHT value <5 and he regularly tested his patients' DHT along with T. My husband's DHT was 7 in May. The MO did not take up our suggestion to prescribe Avodart. By the end of May, PSA was doubling every two weeks.

On 2 July they tested DHT. This time the MO did not ask for us to do it privately. The DHT has increased to 18.2 and PSA 28.2. At the moment, the doubling time is slightly slowed and last Friday his PSA was 55.4 (did not measure DHT as the 2 July result returned to us on 25 July). Now onto Enzalutamide and Avodart along with it.

Going by Dr Myres' statement that DHT is more powerful than T for PCa, it is likely that my husband's cancer is not necessarily hormone-resistant or independent. It is just using a different hormone.

[StayingOptimistic in reply to spw1]

Once we know DHT is high, what should we do about the information? Is there anything we need to do in addition what you already doing up regarding clean diet& excerise? Thanks

[spw1 in reply to StayingOptimistic]

My husband is on Avodart now which is supposed to inhibit Type 1 and 2 5 alpha reductase - the enzyme responsible for converting T to DHT. We are hoping that DHT would have reduced in 6 weeks' time.