Cancer Chemotherapy: How to improve it by greater specificity.

It is not difficult to kill cancer cells; they are pre-equipped with self-digesting caspase enzymes.
The big problem is how to avoid killing too many normal cells, or inducing their self-digestion.

Any difference (pH of cytoplasm, organization of cytoplasm, etc.) can be used for selectivity. Growth rates of cancer cells are not consistently faster than equivalent normal cells.

Nevertheless, most people believe that cancer cells grow faster than normal cells, or even that faster growth rate is what makes them cancerous. (many MDs believe this.)

An even greater majority of people (including oncologists and other physicians) believe that cancer chemotherapy works by selectively killing fast-growing cells. This is not true.

You can find these over-simplifications on pamphlets in oncologists' waiting rooms and on NIH web sites designed to help the general public. The NIH web site used to say that chemotherapy works by slowing down cell growth, rather than by killing cancer cells.


Based of what one sees on TV, anyone would think that cancer treatment is advancing more and more rapidly, steadily closing in on a final cure.

Unfortunately, the truth is that chemotherapy research has been stuck in the mud for decades, despite the valiant work of physicians and nurses. The basic scientists and funding agencies have let everyone down, concentrating too narrowly on identifying oncogenes. Everyone assumed that knowing the genetic causes would somehow make cures obvious. It didn't.

Although chemotherapy saves hundreds of thousands of lives, my own included, improvement has become slower and slower, especially for some kinds of cancer such as pancreas and lung cancer. Most of the drugs used today are exactly the same as were used 20, 30, or 40 years ago.

Most (or all?) of the monoclonal antibodies used in chemotherapy have no known specificity at all for cancer cells. They weren't even designed to be specific. For example, Rituxamib damages all B-lymphocytes, not just the cancerous ones. Avastin and Zaltrap absorb growth factors that regulate development of all blood vessels, not specifically those that vascularize tumors. Therefore they have major side effects (read their web sites) and zero chance of curing anyone, but only slowing cancer down for a few months or weeks, at the cost of an average house. Their prices are decided by estimating the most that people and insurance will possibly pay. Manufacturing costs are cheap, and testing was done on unpaid human volunteers. Drug companies spend much more on advertising than research. Large political donations are made to change patent laws, and to create public beliefs that it is other countries (like India) which have departed from traditions that chemicals are not patentable.

It never occurred to these companies to charge twenty thousand dollars for a shot of anti-snake bite antibodies, although those are more expensive to make than monoclonal antibodies. Imagine their regret, now that they realize what they could have gotten away with.


(#1) We should consider other sources of specificity (such as killing the most anaerobic cells, or killing those with the most disorganized cytoskeletons, or those whose crawling locomotion is least inhibited by cell-cell contact, and every other difference between cancer & normal cells.

#2) We should also ask the source of specificity of the old classic, standard anti-DNA and anti-microtubule chemotherapy drugs (especially cyclophosphamide, other "nitrogen mustards", methotrexate, 5-fluorouracil, doxorubicin, vincristine, vinblastine, cisplatin, and a few others. In fact, these drugs are often more specific than can be explained by growth rates. To improve their effectiveness, it might help to find out how they really work (Perhaps because of defective cell cycle checkpoints, rather than differences in growth rates or division, per se.)

How did medical science get so locked in to the idea that slowing the growth of rapidly growing cells should (for what reason?) kill them, but not kill slower growing normal cells. Would you expect to destroy speeding cars by slowing them down?

a) The great success of Sidney Farber's inhibitors of synthesis of pyrimidines, ("amethopterin" and "methotrexate") for treating childhood leukemia.

b) Side effects of chemotherapy are, indeed, worst for faster growing germinative tissues of bone marrow, skin, hair, and intestinal lining. (Heart muscle is an exception, not understood)

c) Chemicals (mustard gas) that inhibit bone marrow are often effective killers of cancerous cells (especially lymphomas).

d) For lymphomas and leukemias, cure rates are best for the fastest growing sub-types.

I would very much like to hear your thoughts and knowledge on these subjects and phenomena.

The result has been that any chemical that binds microtubules or DNA will be tested on mice with cancer, etc. as a likely new treatment. I don't understand why inhibitors of cytokinesis are not sought.

Reasons for specificity get little or no research funding or attention.

Please open your mind to new and different ideas about possible reasons for specificity, both for existing chemotherapy drugs and for very new kinds of treatments. "Brain storm" the issue. Remember that youth and comparative lack of previous knowledge are advantages for achieving breakthrough ideas. That is really true.

How to kill cells that are less adhesive?
How to kill cells whose contractility is weaker?
How to kill cells that can spread on un-crosslinked silicone fluid?
How to kill cells that can survive in suspension or in agarose gels.

Maybe methods for selective protection of non-cancerous cells? (i.e. followed by heavy-duty treatments that would otherwise be fatal.)

Every difference used for diagnosis of cancer could potentially be used as the basis for a new kind of selectivity, for setting off apoptosis in cancer cells, but not normal cells.

Please notice that continuing to depend on supposedly faster growth rates as the basis of chemotherapy means abandoning the large fraction of patients whose cancers are slow-growing.


Our ability to resist and recover from many viral diseases is achieved by selectively setting off apoptosis just in those cells that contain copies of the virus. Why should it be so difficult to set off apoptosis just in cells with disorganized cytoplasms, reduced contractility, reduced adhesiveness, anaerobic metabolism or other common abnormalities of many cancer cells? Let's everyone quit concentrating so narrowly on just DNA synthesis and microtubules.

And people should revolt against tens of thousands of dollars being charged for cheap monoclonal antibodies; also the news media who fail to explain what is happening, instead of happy-happy, smiley-smiley, jog-for-the-cure. That's not how to win.

Articles and web sites often state the mechanism by which anti-cancer drugs harm cells, but rarely (if ever) suggest reasons for the specificity of the drugs, i.e. why the drug hurts cancer cells more than it hurts normal cells. If you find exceptions, please tell me.

Meanwhile, try as hard as you can to invent methods for selective killing of just cancer cells.



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