Cancer

Causes of Cancer

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

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

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Cancer cells retain many of the properties of whichever differentiated cell type they began from.

A diagnosis of cancer cells in biopsy samples is made by shape and behavior

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]

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Abnormalities of Cancer Cells

The biochemical cause of these phenomena remains unknown, and very little research has been done on it, because it doesn't fit in with oncogene research. The best English language textbook on cancer biology doesn't even mention the Warburg effect. Almost no research has been done about how to kill cancer cells based on either their anaerobic metabolism, or the excess uptake of glucose. (Despite very large amounts of research on how to use the phenomenon to map tumors).

2) Magnetic Resonance Images of cancer cells are visibly different than normal tissues.
This was the subject of the first research paper about MRI. Nobody ever discovered the reason why cancer cells' MRI images are abnormal. Almost no research has been done on the subject.

3) The acto-myosin cytoskeleton of cancer cells is disorganized, and they exert much weaker traction forces as they crawl.

4) Cancer cells can crawl onto less adhesive substrata, from more adhesive substrata. This is a loss of haptotaxis.
It was discovered by Prof. Barbara Danowski, as part of her PhD research in this department. She invented the experiment herself. She then did important research at the University of Pennsylvania, and is now Professor and Chair of Biology at Union College in New York. I had never considered the possibility, until she proved it.

5) Defective cell-cycle checkpoint controls.
For example, cancer cells tend to go ahead and copy DNA, even if it is damaged. Normal cells would delay starting to copy their DNA until damage to it has been repaired.

6) Excessive inhibition of apoptosis.
In particular, 95% of cases of the "follicular" kind of Non-Hodgkin's lymphoma are caused by a breakage and incorrect re-joining of the 14th chromosome and the 18th chromosome, in such a way that the promoter region of the antibody heavy chain gene is next to a gene named bcl-2. This stands for b-cell lymphoma two, because it was the second lymphoma-causing gene to be discovered by looking for chromosome translocations in cancerous lymphocytes of human patients. Nematodes have a gene almost identical to human bcl-2. It is needed to inhibit programmed cell death, both in vertebrates and in nematodes (and probably all animals). Experimenters have even spliced the human DNA sequence for bcl-2 into nematodes, in place of the nematode's own gene. The human gene works fine in nematode embryonic development.

When a human b-lymphocyte has this particular chromosome translocation, it makes bcl-2 protein instead of antibody, and can't undergo programmed cell death. Although such lymphocytes don't grow or divide any faster than normal lymphocytes, they do accumulate without limit. Eventually, they displace your normal lymphocytes and fill up your bone marrow, until you become anemic, can't make antibodies etc. and die.

7) Lack of anchorage dependence, the ability of cells to survive and continue dividing without being spread out on a solid substratum.
Cancer cells can grow and survive suspended in a gel. Non-cancerous cells will undergo programmed cell death if you culture them on an area of substratum that is smaller that the area they normally occupy when attached to a Petri dish.

8) Increased secretion of proteolytic enzymes

9) Loss of differentiated characteristics ("tumor progression")

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How to Cure Cancer: The key goal is selective poisoning.

Examples of what is now available: (I was treated with the underlined ones)

Cyclophosphamide         cross-links DNA strands.

Daunorubicin         intercalates between DNA base pairs

DNA base analogs          get covalently incorporated into DNA

Vincristine         Binds to tubulin; prevents microtubule formation

Taxol         Binds to tubulin; stimulates abnormal microtubule polymerization

Rituximab         A monoclonal antibody against all B-lymphocytes. This was one of the first monoclonal antibodies used for cancer treatment. Many others have subsequently been developed.

Gleevec         Inhibits an over-active tyrosine phosphokinase

QUOTE: (from 2015) "A year's supply of Gleevec (imatinib), a leukemia drug, costs about $159 to make [a year's supply, including a profit margin] , but the yearly price tag is $106,322 in the U.S. and $31,867 in the U.K. A generic version costs about $8,000 in Brazil. ...more than a million cancer patients around the world meet criteria for taking the five TKI pills. "Very few of them are being treated now," he says, because the drugs are so expensive. And the implications stretch way beyond these specific cancer drugs. Overall prices for cancer medications have been going up at a fast clip. Dr. Peter B. Bach of Memorial Sloan Kettering Cancer Center in New York has documented a nearly 100-fold increase in cancer drug prices since 1965 after adjusting for inflation." (QUOTED)

X-Ray irradiation (Minutes per day Mon., Tues., Wed., Thus., Fri. for several weeks)