Embryology   Biology 441   Spring 2011   Albert Harris


Cancer, from an Embryological Point of View



I) The disease cancer results from a cell of your own body changing so that it and its mitotic daughter cells divide and crawl without limit.

It is normal for body cells to grow and divide, and to crawl from place to place.

But cell growth and cell locomotion are normally controlled, by embryological mechanisms, which are only partly understood. When Michael Abercrombie and Joan Heaysman discovered the existence of contact inhibition of cell locomotion, they also discovered that cancer cells in tissue culture have less sensitivity to contact inhibition; that seems likely to be at least part of the reason for their increased invasiveness. Other researchers later used the phrase "contact inhibition" to mean reduced rates of cell growth and mitosis in crowded tissue cultures. Cancer cells are likewise less inhibited than equivalent normal cells.

For many years, other scientists confused these two uses of the phrase "contact inhibition" (inhibition of growth as well as locomotion), assumed the same mechanism caused both, and that cancer cells always lacked both(which Abercrombie never claimed). Then people over-reacted in the opposite direction. The inhibition of locomotion now seems to be caused by prevention of actin fiber assembly near where cells touch each other. Much more research is needed to find out whether cancer cells are more able to continue crawling where they touch other cells, whether this is related to their uncontrolled growth, or if such abnormalities can be targeted by new kinds of chemotherapy.


II) The great majority (>95%) of human cancers are caused by somatic mutations in a few specific genes
(called "Oncogenes").

In many other species, large fractions of cancers are caused by communicable viruses. (examples include cats and turkeys)

Some specific examples of oncogenes.
sis: Codes for a form of PDGF (Platelet Derived Growth Factor). PDGF normally serves as a cell-to-cell signal, secreted by platelets and diffusing to other cells such as fibroblasts and smooth muscle cells, which it stimulates to grow and crawl about. If a cell produces its own form of PDGF, it behaves as if it were being constantly exposed to high concentrations of external PDGF; in other words, it stimulates its own growth and locomotion without limit. This is called autocrine stimulation. It is thought that the sis protein binds to the PDGF receptor proteins while these receptors are in the cytoplasm (prior to their insertion into the plasma membrane where their normal interaction with PDGF would have occurred).

erbB: Codes for an abnormal version of the membrane receptor for the extracellular protein called epidermal growth factor. This form of the receptor behaves as if it were constantly bound to molecules of its growth factor, thus constantly sending a false signal stimulating cell growth. A similar oncogene, called erbB-2 seems (based on its base sequence) to code for a receptor for some other (still undiscovered) growth factor. It is found in amplified form in about one fourth of all human breast and ovarian cancers!

ras: The function of its normal equivalent protein is to relay and amplify stimulatory signals, such as those from growth factor receptors. It binds a molecule of GTP whenever it is itself stimulated. It then relays stimulatory signals and continues to do so until its GTP is hydrolysed to GDP. Certain specific amino acid substitutions eliminate this protein's ability to hydrolyze bound GTP, however, so that it remains permanently in its "on" state, constantly "relaying" non-existent signals for the cell to grow and divide. Such mutations of this one oncogene are believed to be responsible for no fewer than one fifth of all human cancers, including up to half of colon carcinomas, and 90% of cancers of the pancreas! (Although note that several different ras genes are known.) Out of 25 average people, ras will kill one of them!

src: Codes for a protein that spontaneously becomes concentrated on the inside surface of the plasma membrane, especially at the sites of cell-substratum adhesion. This protein is an enzyme (a tyrosine kinase) whose effect is to catalyze the covalent bonding of phosphate groups onto the hydroxyl group of tyrosine amino acid residues of proteins .The proteins phosphorylated by the src protein include some which participate in the mechanical linkage between the actin cytoskeleton and materials to which the outside surface of the plasma membrane attaches; these changes may thus be responsible for weakening the cell's adhesiveness. Recent work in Patricia Maness' laboratory in the UNC Biochemistry Department indicates that the normal form of the gene functions in the chemotactic guidance of nerve growth cones. The src protein was the first tyrosine kinase to be discovered. Since all previously discovered kinases (there are many of them in the cell) had catalyzed the bonding of phosphates to the hydroxyl groups of serines and threonines, it was first assumed that phosphorylation of tyrosines was peculiar to cancer cells. But many normal tyrosine kinases have subsequently been found.

myc: Codes for a nuclear protein whose normal function seems to be as some kind of a transcription factor promoting cell growth. For example, when a normal cell is stimulated to grow and divide (for example, by exposure to PDGF), then the c-myc gene product (protein) temporarily increases in concentration; conversely, this gene normally becomes inactive in non-mitotic cell types. Many human cancers have been shown to have undergone amplification of the c-myc gene (often about 10 copies of the gene) this includes many cases of leukemia and about 30% of lung cancers of the highly lethal "small cell" type and breast cancers. The progression of cancerous cells to ever more and more aggressive states is frequently traceable to further amplification of the myc gene.

bcl-2: This name stands for B cell lymphoma and the protein for which this gene codes seems to have the normal function of inhibiting the spontaneous death of B-lymphocytes. In order that the total number of B cells in your body does not continue to increase without limit (because of constant exposure to different antigens) it is essential that the great majority of B-cells self-destruct. This self-destruction phenomenon ("apoptosis") will be discussed more fully below. When too much bcl-2 protein is produced in a given B cell, this blocks the self-destruction. Trans-genic mice with duplications of the bcl-2 gene accumulate abnormal concentrations of lymphocytes, among other abnormalities. Many human lymphomas result from promoter or enhancer sequences of the antibody genes (on the 14th chromosome) accidentally becoming spliced to the site on the 18th chromosome where the bcl-2 gene is located; whenever these B cells "try" to make antibody molecules, what they make instead is lots of the bcl-2 protein. These cells therefore accumulate to form a slow-growing lymphoma (which is always fatal, although not usually until one of the bcl-transformed clones has subsequently also been transformed by an over-activity of the myc oncogene). Prior to this they grow slowly, making it especially paradoxical that these lymphomas can be caused to shrink almost to nothing by the use of growth-poisoning chemotherapeutic drugs.

* Note that most of the oncogenes listed above are part of a "chain of command" by which external signals, especially protein growth factors, normally stimulate cell growth and division. A typical sequence of events would be for a (A) growth factor molecule to diffuse up to a cell's outer surface, then (B) bind to a membrane protein that serves as a specific receptor for that growth factor, with the conformation (C) or other properties of this receptor being changed by the binding, thereby causing either the activation of a cytoplasmic enzyme (that might be a protein kinase or ), or (D) the activation of a g-protein (such as the c-ras protein) that would then (E) activate a protein kinase, which would phosphorylate various cytoplasmic proteins, including some involved in cell adhesion, and would also stimulate increased transcription and translation of (F) genes for certain transcription factors such as c-myc. Paradoxically, myc also tends to stimulate apoptosis (G), unless counteracted by other gene products such as bcl-2.

Cancer cells from actual patients usually contain over-active versions of several different oncogenes, not infrequently 3 or 4 or more. Typically, there is one that acts at the nuclear level (such as myc) and one or more (such as ras or src) that act at the cytoplasmic level. For several years (between about 1982-86) it was confidently believed that cancer wouldn't occur unless there were at least two, and that one of the two had to be cytoplasmic in its action (like sis, erb, ras or src) and that the other had to act at the nuclear level (like myc). But this is no longer believed.

This department gives a very good course - "The Biology of Cancer" - specifically about oncogenes and how they cause cancer.


III) Several sexually transmitted papilloma viruses cause cervical cancer in women. A vaccine has recently been developed which inhibits infection by these cancer-causing papilloma viruses.

Many newspapers etc. have confused this with 'a vaccine against cancer.'

An editorial in the News and Observer "explained" that the vaccine "Is not yet approved for boys." but doesn't ask "Why not?".

These viruses infect both sexes: but the cancers they cause are in females.

What is their reasoning for vaccinating only one sex? After all, from whom do females catch these viruses?


IV) Cancer cells retain many of the properties of whichever differentiated cell type they began from:

 Carcinomaa cancer of some epithelial cell type
 Adenomaa cancer of some glandular cell type
 Sarcomaa cancer of some mesenchymal cell type
 Leukemiacancer of one of the kinds of white blood cells
 Lymphomacancer of lymphocytes, such as those that make antibodies
 Teratomaa cancer of primordial germ cells
a cancer of undifferentiated nerve cell precursors.
(Once nerve cells form axons, they never divide again)


V) Malignant cancers are invasive (loss of control of cell crawling)
Benign tumors are not (yet!) invasive, but may become so.

Metastasis is transfer of cancer cells from one part of the body to another by breaking free into the lymph or blood (or coelom, or rarely, urine!)

Once cancer cells have begun to metastasize, then it is very much less possible to remove them all surgically.
(Thus, the great importance of early detection)

[Except for lymphoma, etc. which are metastatic very early]


VI) Diagnosis of cancer cells by shape and behavior

Cancer cells are usually somewhat abnormal in shape and structure, as seen under the microscope in histological sections. The well known Pap test depends on this fact, although it uses tissue scrapings rather than sections. It is not unusual for cancer operations to begin with the surgeons cutting out a small chunk of the tumor, then sending it down the hall to the histology lab for quick fixation, sectioning, staining and examination by a skilled pathologist. Just by looking at the shapes of the cells and particularly the shapes of the nuclei, the pathologist is supposed to be able to tell whether the tissue is malignant or not. Often there are 3 options: (1) stitch up the incision, because the tissue is benign; (2) continue with the operation and try to remove as much as possible of the tumor, because it is malignant, or; (3) stitch up the incision, because the cells are so extremely malignant that experience has proven that there is no hope from surgery.

The patient, lying there waiting, and his family members waiting down the hall, might wonder what cellular differences the pathologist is looking for.

Books have been written summarizing the criteria used for this purpose. The quotation below is from "The Cytological Diagnosis of Cancer" by Ruth M. Graham, 3rd. edition Saunders, Philadelphia. (Health Sciences Library QZ 241 G 741 1972 ) page 379:

"Whether a cell is malignant or benign is determined by its nucleus; what type of malignant or benign cell it is determined by the cytoplasm."

"In examining a cell, the microscopist should first look at the nucleus and decide whether it is benign or malignant."

"The first feature to look for is the orderly arrangement of the chromatin. Are the chromatin particles of equal size? Are they distributed evenly throughout the entire nucleus? Is the nuclear border smooth and even in thickness? Does each part of the nucleus resemble every other part? If, in the mind's eye, the nucleus were bisected, would the two halves be mirror images of one another? If the answers to these questions are "yes", then one can be sure the nucleus is benign.

On the other hand, if the answers to these questions are "no"; if the chromatin particles differ in size; if they are distributed unequally at the nuclear border, and in the bisected nucleus no part is a mirror image of any other part, then one can be sure that the nucleus is malignant. "

Note that these criteria are entirely empirical (arrived at purely by experience, not based on any theory or other reason for expecting them). Cells with one set of properties always turned out to be malignant in their future behavior (if not removed), while cells with the other sets of properties always turned out to be benign. Mistakes are sometimes made, even mistakes in the direction of diagnosing malignant cells as benign; but given the amounts of money involved in malpractice lawsuits, it seems noteworthy to me that the quotes above could be so general and sweeping. It is almost as if the weather could be accurately predicted from the shapes of clouds, but no one had bothered to find out the physical causation relating the shapes of today's clouds to the occurrence of tomorrow's storms! There has been little or no research into the question of how cell and nuclear shape is related to oncogene function.

The histological organization of cancer cells is also abnormal; the cells' arrangements as "sloppy": they are irregular in shape, sizes and relative positions, as well as slightly out of alignment. What does this imply about the mechanisms that control cell shape, size, relative position, alignment, etc.? Would you prefer to say that the cancerous state interferes with these mechanisms? Or would you say that malignancy results from the disruption or failure of these mechanisms? Your new ideas might really help treatment.







VII) Cancer cells have many different kinds of abnormalities: (at least this many)

    #0) Abnormally fast rate of growth and division (which may not really be true);

    #1) Defective cell-cycle checkpoint controls;

    #2) Excessive inhibition of apoptosis (bcl-2 causing follicular lymphoma);

    #3) Disorganized cytoskeleton;

    #4) Weakened contractility;

    #5) Lack of anchorage dependence;

    #6) Increased invasiveness;

    #7) Secretion of proteolytic enzymes; (metalloproteases, etc.)

    #8) Loss of differentiated characteristics; ("tumor progression")

    #9) Gain of abnormal combinations of gene transcription;

    #10) Reduced sensitivity to contact inhibition of cell locomotion;

    #11) Reduced sensitivity to contact inhibition of cell growth.

So that is twelve different kinds of abnormalities, and there are more kinds in addition; nobody even knows how many more there are, and almost no research or funding goes toward searching for more.

How many of these twelve abnormalities are targeted by some form of chemotherapy?

Only #0. None of the other eleven is used as a target by any form of chemotherapy, that I know of!

(Although the drugs designed to target #0 probably really work by harming #1, by mistake!)

Certain monoclonal antibodies target all cells of some particular differentiated cell types, the main example being a "humanized" antibody that binds to an antigen produced only by B-lymphocytes (so this one binds to all your B-lymphocytes, the non-cancerous ones just as much as the cancerous ones). Apparently it manages to kill more cancer cells than normal cells, but nobody knows why or how, or if!

You might well think that research ought to be directed toward finding other ways to kill cancer cells, besides damaging DNA and disrupting formation of mitotic spindles. But since the early 1950s, research and funding have become focused entirely on drugs that block cell growth, either by reacting with DNA or by inhibiting formation of mitotic spindles by binding to the protein tubulin. A few variations have been tried, including inhibitors of DNA isomerases. But that is another way of attacking growth rates.

There is little or no deviation from the main dogma, which is that cancer is caused by cells growing and dividing too fast, and that chemotherapy works by selectively blocking DNA duplication and mitosis.

It is easy to check the accuracy of what I have written above; just do an on-line search for "cancer chemotherapy", and read what they tell you on all the sites that you find. They will all tell you that cancer chemotherapy works by targeting fast-growing cells. That's what they all believe.

This is not a fraud or a hoax, or anything like that. Nor is it stupidity. Maybe it is best considered as a form of self-hypnosis. It is analogous to mistakes about the cause of ulcers of the stomach and small intestine. They were thought to be caused by worry and/or by spicy food. The bacterium that actually causes ulcers had been discovered as early as 1899, and then re-discovered in the early 1980s by two Australians (Marshall and Warren), who conclusively proved the true cause by bacteria, which led to an effective cure by a combination of two antibiotics plus an anti-acid. Their discovery was vigorously resisted by nearly all MDs, but won them the Nobel Prize in 2005, and is now universally accepted as true.

What about the evidence that had previously convinced everybody that worry and spicy foods cause ulcers? There never had been any medical or experimental evidence for that mistaken belief. It would have been easy to test, but everyone was so sure they knew the explanation, they didn't consider other explanations.

The same is now true of cancer and chemotherapy.

This is from an actual NIH information web site

You can find it yourself if you search on line, using the target phrase "cancer chemotherapy"

"Medline Plus trusted health information for you"

Here is the quote:

"Normally, your cells grow and die in a controlled way.

Cancer cells keep forming without control.

Chemotherapy is drug therapy that can stop these cells from multiplying.

However, it can also harm healthy cells, which causes side effects."

(The underlining was added by me, to emphasize a common fallacy)

UPDATE: I wrote to the National Library of Medicine about this statement. It has now been changed to read "Chemotherapy is drug therapy that can kill these cells or stop them from multiplying."

As this quotation illustrates, lots of people, maybe most people, even experts at the National Institutes of Health, completely misunderstand the purpose of chemotherapy. The purpose is to kill cancer cells, not just stop them temporarily or slow them down. Why would any sane person make such a silly mistake? A drug that just delays the progress of a fatal disease wouldn't be worth taking, especially if it makes you very sick and is very expensive.

In fact, killing cancer cells is the real effect of chemotherapy drugs, NOT preventing them from multiplying. Furthermore, this killing results from the cancer cells NOT being stopped from multiplying. If they stopped multiplying, that would protect them from being killed. They could wait while the drug was present, and then resume multiplication later; that's what non cancerous cells do, and how normal checkpoint mechanisms protect normal cells from being killed by drugs that damage DNA and block formation of mitotic spindles.

This silly mistake holds back progress toward real cures for cancer. Attempts to discover new and better anti-cancer drugs concentrate almost entirely on chemicals that slow cell growth and division. Unless a chemical slows cell growth, it won't get studied as a possible cancer cure. Slowing of growth is a key part of the bioassays being used to look for cancer cures.

VIII) Chemotherapy

Various combinations of chemicals are given to the patient, usually over a period of months. Because their action is non-specific, many normal cells are also killed. Bone marrow, the lining of the digestive tract, and hair follicles are especially vulnerable, resulting in the common side effects of anemia and immunosuppression, nausea and vomiting, and hair loss.

From the National Cancer Institute web site (http://www.cancer.gov/cancertopics/coping/chemotherapy-and-you/):

"Chemotherapy works by stopping or slowing the growth of cancer cells, which grow and divide quickly. But it can also harm healthy cells that divide quickly, such as those that line your mouth and intestines or cause your hair to grow. Damage to healthy cells may cause side effects. Often, side effects get better or go away after chemotherapy is over."

From the American Cancer Society web site (http://www.cancer.org/Treatment/):

"Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell."

"Depending on the type of cancer and its stage (if and how far it has spread), chemo can be used to:

Cure the cancer.
Keep the cancer from spreading.
Slow the cancer's growth.
Kill cancer cells that may have spread to other parts of the body.
Relieve symptoms caused by cancer."

From http://www.medicinenet.com/chemotherapy/article.htm:

"How does chemotherapy work?

Chemotherapy works by stopping or slowing the growth of cancer cells, which grow and divide quickly. But it can also harm healthy cells that divide quickly, such as those that line your mouth and intestines or cause your hair to grow. Damage to healthy cells may cause side effects. Often, side effects get better or go away after chemotherapy is over."

From http://chemotherapy.com

"Chemotherapy works by destroying cancer cells; unfortunately, it cannot tell the difference between a cancer cell and some healthy cells. So chemotherapy eliminates not only the fast-growing cancer cells but also other fast-growing cells in your body, including hair and blood cells. Some cancer cells grow slowly while others grow rapidly. As a result, different types of chemotherapy drugs target the growth patterns of specific types of cancer cells. Each drug has a different way of working and is effective at a specific time in the life cycle of the cell it targets."

Examples of Current Methods of Cancer Chemotherapy:

Cyclophosphamide - "nitrogen mustard" (chemical relative of "mustard" war gasses used in World War I), an alkylating agent that binds to DNA and cross-links it. [Note that the Wikipedia article on cyclophosphamide says "It is a chemotherapy drug that works by slowing or stopping cell growth."] In addition to the usual side-effects common to many chemotherapy agents, it can cause bladder damage, including carcinoma of the bladder, and temporary and permanent sterility.

Vincristine - binds to tubulin dimers, inhibiting microtubule assembly; prevents formation of the mitotic spindle. Specific side effects include damage to nerves, including ability to walk, and hyponatremia (abnormally low sodium levels in the blood).

Daunorubicin (which is called by several different names, including adriamycin) - intercalates between bases in DNA. It permanently damages the heart.

Prednisone - a corticosteroid and immunosuppressant; included in chemotherapy combinations but its effect isn't entirely clear. From the American Cancer Society web site: "For example, prednisone helps prevent white blood cells from traveling to areas of the body where they might add to swelling problems (such as around tumors). It also seems to help with the treatment of certain blood cancers (such as leukemias) by causing some cancerous white blood cells to commit suicide." Side effects include kidney damage, osteoporosis, type II diabetes, and glaucoma.

Rituximab - monoclonal antibody against CD20, a surface protein of B lymphocytes. It attacks ALL of a person's B-lymphocytes, thereby severely reducing the normal immune response and making the patient vulnerable to infections.


Notice the lack of specificity of any of these categories of treatments.
None of them is even designed to kill only cancer cells.

Also notice that monoclonal antibodies aren't really drugs, but are medically equivalent to the passive immunity anti-snake bite injections. They were invented by British government researchers in Cambridge, England. No U.S. corporations had anything to do with their development.



Look at the crystals of tubulin in the cytoplasms of these cells:

Original photograph of about 5 mesenchymal cells in tissue culture, which have been treated with the anti-cancer drug Vinblastine, and then fixed and stained with a fluorescent antibody that binds specifically to tubulin, the protein that microtubules are made of. Vinblastine has the special property of causing tubulin to precipitate into comparative large, micrometer-sized three-dimensional crystals in the cytoplasm (i.e. instead of polymerizing into microtubules).

(This tissue culture and staining was part of PhD thesis research by Prof. Barbara Danowski and John Dmytryk, helped by Ms. Patricia Greenwell.)

It is assumed that the anti-cancer effectiveness of vinblastine, vincristine and SOME other anti-tubulin "spindle poisons" is because they prevent formation of mitotic spindles, which in turn is believed somehow to be more likely to kill cancer cells than to kill normal cells, because (supposedly) the cancer cells divide more, or faster, or something.

You will embarrass and annoy the "cancer experts" if you ask simple questions like the following:

a) Colchicine binds to tubulin and prevents mitotic spindle formation just as well as vinblastine, but doesn't kill cancer cells; why not? What is even a possible reason why not? Why is no research done on this?

b) You can easily prevent metaphase by mechanically squeezing tissue culture cells (because of normal checkpoint controls), but that doesn't kill cells, much less kill cancer cells more than normal cells. Why not?

c) Why should fast-growing, frequently-dividing cells be harmed more than normal cells by drugs that block mitosis?

d) Vinblastine, colchicines and most other tubulin-binding drugs cause increased polymerization of fibroblasts' myosin, and more than double the force of cell traction, probably because of release of a GTP transferring protein, which transfers more GTP to some Ras-like proteins. Could this category of effect be how some of these drugs harm cancer cells? (i.e. instead of by blocking mitosis)

Chemotherapy isn't exactly "rocket science". A more accurate description would be "stumbling around in the dark", clinging to 50 year old guesses that never made sense, for lack of anything better to try. This is not to deny that chemotherapy actually works; It just doesn't work very well, besides producing horrific side effects, and being based on wild guesses made 50 years ago, and mostly disproved since then.

We biological researchers have betrayed the trust of cancer patients, and the nurses and physicians who treat them. That's the bad news; the good news is that clear thinking by students like you may either find much better treatments, or ways to improve current treatments.


IX) How to kill cancer cells without killing too many normal cells.

Like almost everyone else, I expected that when the causes of cancer were completely understood at the molecular level then we would see how to cure it.

So far, however, this information (about oncogenes, etc.) has not been useful for curing patients. What is needed are methods to kill just those cells in which oncogenes are over-active.


The goal is to kill cancer cells; not to make them more normal, or to slow down their growth. To kill them, it is better to magnify their abnormalities.

Any and every one of those abnormalities in the list above can be turned into an "Achilles heel" against cancer.

Unfortunately, research has become bogged down, concentrating of poisoning DNA synthesis, mitotic spindles and a few oncogenes.

The available drugs are slowly improving, but rarely cure, make patients very sick and get sold for astronomical prices. (Often hundreds of thousands of dollars per patient; no kidding.) Hardly anybody realizes how much money is charged, especially for cheap, easy-to-make monoclonal antibodies.

Profits are so gigantic, there is no economic motive to find real cures for cancer, so hardly anyone is even trying.

No drug is even tried on people unless a pharmacy manufacturer decides to pay the millions of dollars of expenses for the tests, and thousands of patients bravely risk their lives.

This situation can be made to sound very generous on the part of the pharmaceutical manufacturers, paying for the human tests.

But it's really no way to run a railroad. Think about it! It gives manufacturers veto powers over directions of research, and they have less than zero economic motivation to find real cures.

(Which could, and probably would, bankrupt them.)


Selectivity is the problem: There is no difficulty just killing cells.
In general, cancer cells are harder to kill than normal cells:
(for example, when cells die because of poor tissue culture conditions, cancer cells survive bad culture conditions, acidic medium, exhausted media, and will be the only survivors of mixtures of cancerous and normal cells.
Cancer cells also require much less serum, only 1% or 2% instead of 10%)

Every consistent difference between cancer cells and normal cells potentially can be made into a method for selectively killing cancer cells.

Cancer cells differ from the closest normal equivalents in many different ways - mechanical differences, shape differences, growth rates, exertion of forces on collagen, etc.

Unfortunately, since about 1950, research has concentrated on the over-simplification that cancer cells grow and divide more rapidly than normal cells. This mistake holds back discovery of cures.

This mistake has been combined with an illogical assumption that if a particular chemical poison damages DNA or inhibits mitosis therefore it should kill faster-growing cells, more than slower growing cells.

In fact, for unknown reasons, this is often true:
Faster growing cells are harmed more by inhibitors of DNA synthesis or mitosis.
Therefore people forget that it makes no sense.

If you speeded-up slow-growing cells, would you expect that to kill them?
Then why do you expect fast-growing cells to be killed by slowing them down?

Another illogical belief is that cancer cells should be killed by drugs that selectively block enzymatic effects of over-active oncogenes.

For example, a certain drug selectively blocks an abnormal kinase coded for by a certain chromosome translocation ("Philadelphia chromosome" fusion protein). A particular kind of leukemia is caused by this abnormal kinase.

Although it makes sense that blocking this kinase should temporarily cause the leukemia cells to behave like normal cells, it doesn't make logical sense that the leukemia cells are killed by blocking this kinase.

It is not normal for cells to have this enzyme, anyway; therefore what sense does it make that blocking the enzyme kills the cells.

Why does almost everyone think this makes sense? Many people also believe that jets and rockets are propelled by their exhaust pushing against the atmosphere. "Common sense" is often misguided.

The true explanation may be that apoptosis is somehow being inhibited by the kinase (in addition to the stimulation of growth by the kinase).

At least that would be logical. It might also help to explain why leukemia isn't actually cured by this drug, although death is delayed by about 2 years.

The goal is not to make cancer cells more like normal cells.
The real goal should be to magnify their abnormalities, enough that these abnormalities kill the cancer cells, rather than killing the person in whose body the cancer cells are living.

Unfortunately, most cancer researchers are notoriously second-rate scientists.
You can do better.

The clinicians, the physicians who treat cancer, include the best in the world.
It's too bad the researchers are not any where near as good as those treating this disease.

Furthermore, much less money is spent on cancer research that on attempts to cure diseases that kill only a fraction as many people. The "War on Cancer" was a cynical shell game in which funds that had already been appropriated for medical research were transferred from one spending category to another.

The percentage of approved grants that actually get funded is lower for cancer than for any other category of diseases, and this has remained true for decades.

Financially, there are not enough motivations to seek actual cures, which kill the goose that lays the golden eggs.
Improved treatments will not bring in more money than the drugs now being used.

Nevertheless, tens of thousands of Americans are actually cured by chemotherapy every year, and tens of thousands of others have their life spans lengthened by year or even decades.


How you might invent a new cure for cancer!
Always keep in mind, the key problem is specificity


Initiation of Apoptosis Abnormalities of cancer cells
i) Caspase enzyme activation a) Over-activity of certain kinases
ii) Non-self, viral-like peptides
b) Excessive phosphorylation of certain proteins
(held by type I histocompatibility antigens)
iii) Fas/Fas ligand stimulation c) Mutated GTPases, unable to hydrolyse GTP
iv) Other damage to cells?
d) Anaerobic metabolism
e) Inability to halt at cycle checkpoints
f) Lactic acid production
g) Secretion of proteolytic enzymes
h) Disrupted cytoplasmic actin
i) Abnormal adhesions
j) Less fibronectin secretion

Blocking the activity of oncogenes doesn't really do you any good. You have to kill just those cells in which the oncogenes are causing cancer.

That is so important to remember; let me repeat that:

You have to kill just those cells in which the oncogenes are causing cancer.
You have to kill just those cells in which the oncogenes are causing cancer.
You have to kill just those cells in which the oncogenes are causing cancer.
You have to kill just those cells in which the oncogenes are causing cancer.

You have to kill just those cells in which...    don't forget.

At current rates in the USA, 25% of you will get cancer.

Four-fifths of this 25% will die of their cancer.

That's 20 people out of every one hundred.

You have to kill just those cells in which...         What was it, again?

Within living memory, tuberculosis used to be nearly incurable, killed more Americans per year than cancer, and had the same reputation as cancer for inexorable killing. Tuberculosis was what killed Anton Chekhov, Robert Louis Stevenson, the mathematician Riemann, all 4 Brontes, Chopin, Emerson, Kafka, Keats, D.H. Lawrence, Thoreau, Thomas Wolfe and George Orwell, most around age 40. A diagnosis of tuberculosis used to be an inexorable death sentence, but this disease then became almost completely curable with the drugs streptomycin and isoniazid. Unfortunately, Reagan's public health cutbacks (right-wing!) during the 1980s, combined with (left-wing!) soft-headedness toward forcing medical treatment and quarantine of "The Homeless", resulted in production of incurable strains of tuberculosis (because poor patients took too little of the drugs to kill all their germs, but enough to select for mutant germs less susceptible to these drugs). Tuberculosis now kills several thousand Americans per year & well over one million per year world-wide!

Will cancer ever become as curable as tuberculosis did? Maybe you can help make it so. Somewhere, there are weird little facts about cancer cells, that don't seem important because nobody has had the imagination to see how to take advantage of them to kill cancer cells while not harming normal cells. What is lacking is someone with the patience to collect such odd and useless facts, the imagination to figure out how to put these facts to use, the energy to develop methods for using these facts, all combined with the stubbornness not to give up along the way. This person might be you.
Since it is the cancer cell that is abnormal and defective, justice requires that it should die, not you. It is kind of ridiculous that developing the wrong kind of defectiveness in just one of your trillion-plus cells should be fatal to you. We need to find ways to make these kinds of cellular defectiveness fatal for the individual cells that possess them, instead of being fatal for your whole body! Keep this in mind: The goal is find drugs or other treatments that are more poisonous for cancer cells than they are for normal cells!

THINK for the cure!



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