https://en.wikipedia.org/wiki/Asparaginase#As_a_drug
https://en.wikipedia.org/wiki/Bcr-Abl_tyrosine-kinase_inhibi...
For "solid" tumor cancers like breast, pancreatic, prostate, and skin cancer, we're still struggling to make a dent in the death rate.
Actually, we are not "struggling" on breast cancer. The death rate comes down a reasonable percentage each year.
It's just that a small percentage compounds slower and slower once you take out the low hanging fruit.
As you point out, the problem is that cancer isn't just one disease with one mechanism. Even "breast" cancer isn't just one disease with one mechanism.
So, it's not terribly profitable to go after say "cancer X with mutations P, D, and Q". This really needs government funding.
We'd have been far better off with a governmental "War on Cancer" than on any of the other "War on X" that they've done.
This is one of the key problems. The effective size of most true cancers types is so small that pharmaceutical companies can’t make a profit developing a drug that targets these cancers. Imagine you identify a new drug that 100% cures people with a cancer that has three specific mutations. Now lets assume that out of the millions of people who get cancer each year only 500 have this particular combinations of mutations. This drug will cost the same as any other drug to develop (lets assume $1 billion), but you can only sell it to 500 people per year. Even if you set the price at $100,000 per person you don’t come close to earning enough money to pay back the development costs. Add in the fact that very few drugs make it through the whole development process you can see why we have a problem.
1. Enrolling enough people in a trial to prove you can cure with a combination therapy
2. Evolved resistance with an entirely new set of mutations
The current thinking is that cancers are not evolving for resistance during treatment, but that there are a sub-population of cells present in the tumour mass that are being selected for by treatment (i.e. we kill 99% of the tumour that is sensitive and the 1% that is resistant grows back).
We know how to solve this problem from HIV. HIV evolves resistance to drugs faster than any cancer yet we can treat patients for years by using HAART (i.e. give lots of drugs at once that target different key components). We need to do this with cancer, but this will require developing new drugs that are less lethal since you can't just give a patient a dozen standard anti-cancer drugs and expect them to live.
No, the cancer evolves resistance during treatment. Evolution is change in allele frequency in a population over time, not the emergence of new mutation. It does not matter whether the mutation was a rare, preexisting mutation or it occurred after treatment; both likely happen. The "evolution" part is the outgrowth as a result of a fitness differential produced by the new environment (therapy).
>We know how to solve this problem from HIV. HIV evolves resistance to drugs faster than any cancer yet we can treat patients for years by using HAART (i.e. give lots of drugs at once that target different key components). We need to do this with cancer, but this will require developing new drugs that are less lethal since you can't just give a patient a dozen standard anti-cancer drugs and expect them to live.
We will never be able to do this with cancer. HIV has only nine proteins in its genome. This means any resistance mutation it develops must be on-target and will tend to operate through specific bottleneck points. This is not true with cancer - there is on-target resistance, of course, but this is easily overcome through better drug design. We can develop drugs that get around EGFR T790M, but in a cancer there are a dozen different new mutations in other genes that can emerge to produce resistance. Drugging all of these targets in advance is impossible - we can barely drug one gene with patients tolerating it. We'll lose this game of whack-a-mole.
This is a losing game in general. The tumor has too much space to adapt - it's not limited to a tiny genomic space like HIV, it has the whole human genome to work with.
This is why I think successful strategies are going to result from not inhibiting particular genes but treating the tumor as a tissue and modulating the host/tumor interactions. Immunotherapy acts on this axis, and it's already looking more promising in this regard (responders don't tend to become resistant).
>Drugging all of these targets in advance is impossible - we can barely drug one gene with patients tolerating it. We'll lose this game of whack-a-mole.
It is not impossible, just difficult. It will certainly be impossible if we keep trying to develop new treatments the way we have for the last 50 years. We need to change the entire way we screen and test new cancer treatments if we are going to be able to use the HAART approach in human cancer.
I agree with you that immunotherapy is looking the most promising approach right now, but done right chemotherapy has a lot of potential too. I would not rule one or the other out.
And sometimes there are other diseases caused by problems in whatever pathway you're messing with. Tamoxifen, for example, can be used to treat two relatively rare non-cancer diseases.
One way to workout how many different cancers there are when classified by treatment response is to look at the true cure rate to when a cancer is treated using a treatment. Since the treatments we have are biased in targeting the most common sub-types this can only give us a lower bound, but even this number is huge since the cancer cure rate is not that high for the most common cancers (I am not talking about 5 year survival, but real cure). My rough guess is there are 10,000s of different cancers when classified by treatment response.
Well, sure. That's my point, though. Cancers that arise indifferent parts of the body may be treatable with the same drug.
>One way to workout how many different cancers there are when classified by treatment response is to look at the true cure rate to when a cancer is treated using a treatment.
That's the current situation as it stands today. It's not necessarily what we'll see in five or ten years.
Having said this the most hopeful area is the immunotherapies. Scaled out to their full potential we could have a very powerful set of drugs to go after the cancer diversity problem.
A more effective approach would be to find ways to reduce the cost of new drug development.