Why can't pharmaceutical companies find a cure?

[nec209]

I mean the pharmaceutical companies spend billions of money every year trying to find a cure for diseases, illnesses ,virus,parasites,HIV and cancer so on.

 

How long will this take or where there be a cure?Have they not tried every drug combinations or how many drug combinations are there ?Like is it thousands , millions or billions?

 

Why no cure for lung cancer ,breast caner ,liver caner ,HIV or other cancers so on?

 

How are drugs made ?Do they use math to come up with drugs? Or try different combinations or use organism to kill diseases or illnesses ?

 

I really have no idea how the pharmaceutical companies work or go about looking for a cure or how conplex the problem is.

[D H]

Cancer is a general descriptor of a whole slew of different symptoms. It is not a specific symptom, let alone a specific disease. There is no magic bullet.

 

A lot of medicines used to fight diseases are poisons. They are poisonous to the disease-causing agent -- and to us. A lot of candidate cures that kill disease-causing agents in test tubes kill the patient as well. Not good. A lot of those that don't kill us in small doses don't cure the disease in small doses. A lot that kill the disease in a test tube environment don't kill the disease in humans (or in test animals) because our active chemistry alters the medicine.

 

Pharmaceutical companies reject many potential candidates because they are too poisonous, they don't work at all in vivo, because they work, but only slightly. They reject even more because they can't figure out how to manufacture the medicines in bulk.

[nec209]

Cancer is a general descriptor of a whole slew of different symptoms. It is not a specific symptom, let alone a specific disease. There is no magic bullet..

 

Yes every cancer has different symptoms but basic of what cancer is cells gone bad replicating and taking over.

 

 

 

 

A lot of medicines used to fight diseases are poisons. They are poisonous to the disease-causing agent -- and to us. A lot of candidate cures that kill disease-causing agents in test tubes kill the patient as well.

 

What do you mean bt agents .Can they not come up with a drug that is not poisonous .

 

 

Not good. A lot of those that don't kill us in small doses don't cure the disease in small doses. A lot that kill the disease in a test tube environment don't kill the disease in humans (or in test animals) because our active chemistry alters the medicine.

 

So they have to find a way so the drug is not alter by the body chemistry .

 

Pharmaceutical companies reject many potential candidates because they are too poisonous, they don't work at all in vivo, because they work, but only slightly. They reject even more because they can't figure out how to manufacture the medicines in bulk

 

 

The idea how the pharmaceutical companies go about looking for a cure is conplex .Do they use math or different combinations ?

[SkepticLance]

Lots of drugs cure diseases. Antibiotics cure bacterial diseases. Antifungals cure fungus caused diseases. Many other drugs kill parasites and cure diseases caused by parasites. There are drug anti-cancer treatments that result in cures of a few cancers, though many cancers cannot be successfully cured in this way.

 

Incidentally, the first cure of AIDS has happened, though not by drugs. A sufferer also had leukemia, for which the treatment is a bone marrow trnsplant. Some people have been found to be immune to AIDS, by virtue of having two copies of an immunity gene. In this case, a bone marrow donor was also immune to AIDS. The AIDS patient had his own immune system destroyed by radiation, and replaced with the bone marrow transplant, that included the immune genes. The AIDS patient had a double recovery. Cured of both leukemia and AIDS.

 

This opens hope for AIDS cures by gene therapy. Not a drug, but nevertheless, a cure.

[DrDNA]

Yes every cancer has different symptoms but basic of what cancer is cells gone bad replicating and taking over.

Saying that the problem is simply that the cells have gone bad is akin to saying that my car has gone bad (but much more complex).

For example, there could be 100's or 1000's of reasons why my car has gone bad; but many more of reasons why a cell has gone cancerous.

 

 

 

 

 

What do you mean bt agents .Can they not come up with a drug that is not poisonous .

In general, the main difference between a drug and a poison is dose.

And trying to specifically target cancer cells, which are derived from otherwise normal cells, without killing too many normal cells, is not trivial.

It is sort of like adding a substance to your aquarium that will kill all of the spotted goldfish, without harming all of the uniformly colored goldfish.

 

 

So they have to find a way so the drug is not alter by the body chemistry .

 

The idea how the pharmaceutical companies go about looking for a cure is conplex .Do they use math or different combinations ?

 

Yes. Yes. Yes and Yes.

[GDG]

They reject even more because they can't figure out how to manufacture the medicines in bulk.

 

In my experience, this is relatively rare. If it is difficult to manufacture, it just costs more. Obviously, nothing that cannot be synthesized ever gets tested

 

• A typical drug discovery program first settles on a molecular target: e.g., a receptor, a cytokine, an enzyme essential for a pathogen's survival or spread, etc.
  
• Compounds that interact with the target are designed or identified. If successful drugs for that target are already known, new drugs may be designed by comparing the morphology of several successful drugs. Otherwise, one can identify potential leads by screening compound libraries or fragment libraries for anything with activity. Then, more compounds are designed based on the screening results.
  
• After several compounds having activity are made and tested in vitro, further variations are designed and synthesized in an attempt to increase the activity (and/or reduce side effects and undesireable properties, like rapid excretion or metabolism). Each lead may result in a group of several hundred or thousand compounds having a related structure.
  
• Likely candidates are selected from those groups, and are tested in animals. Due to the expense of conducting trials, typically only 1-3 compounds are selected for preclinical trials.
  
• The compounds that were not selected are not discarded, but are added to the company's compound library, where they will get screened periodically for activity against other targets.
  

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So they have to find a way so the drug is not alter by the body chemistry .

 

Well, this is the hard part. Your body has a large set of enzymes that metabolize foreign compounds. Some enzymes look for aromatic rings, and oxidize their substituents. Others latch onto free OH groups and attach a glucuronic acid group. Frequently, these modifications destroy the activity of the drug, and/or cause it to be rapidly removed from the system.

 

In some cases, it is possible to substitute another substituent for the group that was affected. Sometimes, the new group simply activates a different enzyme, and there is no net gain. Sometimes, it turns out that the group is essential to the activity of the drug, and there is no way to replace it while maintaining activity. In other words, sometimes it is simply not possible to prevent the drug from being modified by "body chemistry." In such cases, one generally starts over with compounds having a different basic structure.

 

There are a few compounds that specifically inhibit particular CYP enzymes. However, we did not evolve CYPs just to make it difficult to design drugs: these enzymes are required for your basic metabolism and deactivation of toxins found in the environment (and in your food). Knocking out CYPs so that your drugs work is likely to cause more problems than it solves (acceptable only in life-or-death situations).

[Fedace]

Actually, we are much closer to curing Cancer than we were 20 years ago. Cancer is caused at the DNA level and gene sequencing gone wrong and so on. So to find a cure, it is not as simple as finding a drug that works for all cancer types. That is pretty much impossible. Gene therapy one day will cure cancer by turning off the gene that is out of control and telling the cells to stop dividing endlessly. There are some advances in Targeted drug therapy. As in you piggyback the chemotherapy onto a antibody and let it attach to ONLY the cancer cells and leave the healthy ones alone. That is promising. and that will limit the toxicity significantly.

but only real cure will come from genetic research where one day they will be able to manipulate the gene so that they can literally repair the DNA or the Gene that has gone haywire.

[GDG]

Yes, there have been significant advances in treating cancer over the past few decades. However, it is not as simple as all that. First off, cancer is typically not the result of a single gene gone haywire: there are a number of checks that have to be circumvented before the cell becomes neoplastic. For example, the cell has to lose contact inhibition, lose cell cycle regulation, and has to overcome the p53 program that causes apoptosis if there is a problem in replication. Frequently, tumor cells also secrete angiogenic factors to induce blood vessel formation (otherwise they starve), and tumors that become metastatic must also express the proteins that allow them to pass through blood vessel walls and into the circulatory system (and back out again).

 

Also, tumor cells do not necessarily express a unique marker protein. Consider where those proteins have to come from: they are all already encoded in the normal patient's genome. You may find that the surface protein that characterizes the tumor also characterizes certain other normal cells. Plus, targeting that surface protein (even when it is essentially unique, e.g., it is a fetal antigen not normally expressed in the adult) can drive selection of tumor cells that do not express the antigen. It sometimes happens that the tumor shrinks by half, and then comes back when the cells that were not expressing the antigen proliferate and take over.

 

Unfortunately, cancer is something that could easily keep up busy for decades to come

[nec209]

I think the past 2 replies should have been posted in the thread understanding cancer.

 

But I'm really trying to understand how drugs are made and how pharmaceutical companies go about looking for a cure.

[ennui]

It's a pretty straightforward process. Let's pretend a disease is caused by protein X, a cellular receptor which has a gain of function - you need to suppress its activity.

 

1. Find the protein or gene responsible. Map to the right chromosome. Clone it so you can experiment on it.

2. Use NMR or X-ray crystallography to determine its structure. Needs to be purified first.

3. Ask a chemistry lab to design an inhibitor.

4. Build a library of inhibitors and use molecular dynamics (MD) simulations, etc. to see which one matches best.

5. Synthesize this inhibitor and test it in vitro. If it works, step 6.

6. Mutate protein X in a mouse model, essentially giving the mice the disease. Test the inhibitor on them. This is in vivo testing.

7. Assess the toxicity of the drug inhibitor - do they have side-effects?

8. Do more testing, refine the drug using biophysics.

9. If it works and there are no serious problems, move on to a human model.

10. Apply for FDA approval, and do all the Phase I, II and III trials.

 

This is a gross simplification and there are many variations in this process. But this is a hypothetical scenario of how a drug might be designed and tested. You can see how it pulls together the skills of molecular biologists, biochemists, structural biologists, biophysicists, geneticists, immunologists, pharmacologists, organic chemists, etc.

Edited March 3, 2009 by ennui

[DrDNA]

1. Find the protein or gene responsible. Map to the right chromosome. Clone it so you can experiment on it.

 

Nice post.

 

You listed what I will refer to as

1a. Targeted Drug Design.

 

To elaborate further, we also have:

 

1b. Natural Product Chemistry or Pharmacognosy (a term not used much any more, but I still like it ).

Which is isolating and screening compounds from for example, plants and marine organisms.

Taxol is a good example.

After the natural products are characterized, synthetic routes are usually devised in order to scale up production.

In some cases, the structures of the compounds are modified to optimize activity and specificity.

 

1c. Combinatorial Chemistry. Synthesizing thousands of compounds and screening them for activity.

Then selecting the active compounds for further screening.

[nec209]

Wow I did not know there was so much Chemistry .

 

That takes care how they look for a cue but does not explain the conplex of the problem or why it takes so long for cure .

 

It is not snap there is problem in 2 years there is cure it takes years and years some times 40 years to cure comes out.It is very conplex.

 

I'm going ask for some web sites on the human body chemistry ,make up ,drug design.