[xiphias2]

Hi Jose, thanks very much for working on this!

My girlfriend had breast cancer twice already, and actually I was quite scared that she told me that she would almost rather die thank go through chemotherapy again, it was so bad for her (she's been through more than 15 operations, but she doesn't care about that). Currently it looks that she can't ever stop taking anti-estrogen drugs ever in her life even though it has lots of side effects.

My question is: most of the drugs fail at one of the trials with much more than 90% probability. What is the chance you give your drug to be succeeding, and how did you get failure rate probability under that 90%? Also what's plan B?

[mejiaoneto]

Sorry to hear about your girlfriend. I have heard those feelings as well. They are not uncommon. The probability of success changes as you move further in the development. Below there is a link for a booklet that talks about the general pharma odds in page 53.

In our particular case, we took a known chemotherapeutic agent called doxorubicin. It has been used for the last 40 years in about a dozen types of tumors (include certain types of breast cancer).

The problem is that 3 out of every 4 patients end up major side effects to their immune system (e.g. neutropenia), but even worse, you can only take about 6 doses in your whole life, otherwise your risk for cardiac damage increases very rapidly. It is known colloquially as red death and red devil, because of its red color.

Using that drug as the starting block for our approach improves our probability of success and helps us know what to expect in terms of side effects.

[AnthonBerg]

I’m sorry. We’ve been through breast cancer and anti-estrogen therapy. It’s hard.

[xiphias2]

The problem with my girlfriend is that she thought she went through it, but after 4 years she stopped anti-estrogen therapy because she wanted a baby, and 1 year later her breast cancer got metastatic.

After new extremely complicated surgeries where most surgeons said that it's impossible to get the tumor out of her body (there was only 1 surgeon who took the chance), now she's back on anti-estrogene therapy and it seems that she can't ever stop it again in her life, or at least until some better therapy is available.

I'm quite hopeful of the liquid cancer biopsies though, detecting the small amount of early stage cancer DNA inside the blood will get useful as the thoughput of DNA sequencing increases exponentally, but the cancer curing trials look promising as well.

[mejiaoneto]

I am sorry to hear that.

With regards to your point about liquid biopsies.

To have a minimally invasive sensitive and specific test would be a great addition to the toolbox against cancer. However, if it comes back positive, then what comes next? Maybe surgery? But if we had therapies that were highly effective and could concentrate the cancer drug at the tumor with minimal side effects that may be preferential or supportive to going through the operating room, anesthesia and necessary morbidity of surgery. And potentially you could do this multiple times if needed.

[xiphias2]

To take my girlfriend as an example, she found her tumor in time when it could have been managed probably without chemotherapy, but as she was only 30 years old, the doctor said that it's probably not tumor and that she should go back 1 year later. Now of course BRCA mutation testing is much more known and available, but this was 10 years ago.

The reason why I'm more hopeful about liquid biopsies than greatly improved cures at this point is because it depends on an informational technology that is relatively predictable, and has a high chance of success for many types of cancer at the same time. Testing has 0 side effects, and can be done for $2000/year in a few years, as the providers are not planning to go through insurance companies first. Also it can be launched globally as long as the blood withdraval can be taken care of.

Shasqi's goal sounds amazing, but it needs to go through all the clinical trials, it has to be covered by health insurance, which takes much more administration work, it has a 10% chance of success for the first time (as it's in stage 1 trial right now), and will take at least about 5-10 years to succeed for just 1 type of cancer, even if it's an extremely important type.