ONCOGENES:  Cancer is the result of a series of mutations that confer on one cell line (from a single cell) a number of properties for which various biological constraints have been modified.  The process is one of genetic alteration via mutations that alter the DNA of a gene or through gross alteration of chromosome (see #9 below).  A Gene that contributes to making a cell-line cancerous is called an oncogene.  The unchanged, normally functioning, version of that gene is called a proto-oncogene.   There are 12 general types of functional alterations (and thus 12 genetic changes[i]) that contribute to turning a single cell line into a life-threatening cancer; however, not all 12 must be present.

1.  Turning on of the chemical signal which causes a cell to rapidly divide.

2.   Turning off of the chemical signal which turns stops a cell from rapidly dividing. 

3.   Stimulate the formation of new capillaries to assure adequate oxygen supply for continued growth.

4.   The cell line must avoid senescence which occurs at around 50 to 70 generations, and thus become immortal.  To do this it must curtail the telomerase control upon the number of divisions.[ii]  

5.   Invade adjacent tissues:  Most organs are enveloped in a membrane (muscles and lungs).  Most cancers fairly early develop the ability to grow through the membrane and invade adjacent tissues. 

6.  Metastasize:  have microscopic colonies of the tumor relocate in other sites.  It must, in most cases, spread from its primary tissue to distant sites.  This involves sometimes a mutation affecting adhesiveness[iii] and sometimes also the markers on the cell wall.[iv]  Over ninety percent of cancer deaths are due to metastases.

7.   Be able to both enter and leave blood vessels like the way lymphocytes do by secreting a factor which allows them to enter a capillary and then at another site to pass out of the capillary again by secreting this factor, a class of compounds know as Src kinase. 

8.   Some cancers have abnormal DNA due to gross changes in the chromosome that consist of translocation, duplication, deletion, or inversion.[v]  This type of abnormality results in the imperfect expression of genes on that chromosome.

9.   Another way to speed up the timetable is the disabling of the gene which functions in mechanism that checks during cell mitosis that accurate replication in the new chromosome of the DNA has occurred.  Several such genes, such as P53, have been identified. When disabled the risk of cancer in the cell types that rely upon that gene will increase several fold.  If the factor has been inherited the cancer type will be common among relatives and often can occur unusually early.  P53 is associated with breast and several other types of cancer. 

10.  Excrete growth factors which enable the cancer to attract stem cells which then help support the growth of the tumor by stimulating the growth of capillaries and other structures needed to support a large tumor.  This is a new finding, one which explains the failure of treatments for some patients.

11.  Express any of a number of genes which give stem cells their unique properties.  This is a new finding, one which explains the failure of treatments for some patients. 

12.  Methylation of the DNA, which primarily occurs during embyogenesis and development, has been associated with inaction of tumor suppressor genes.  This occurs when the abnormal methylation alters a gene responsible for the checking of the accuracy of the DNA replication.

Oncogensis:[vi]  The process in 2 occurs two ways, either by a defect in the DNA of one particular cell line or by the inheritance of a defect in a gene such as P53.  Inheritance accounts for no more than 10% of all cancers.  Such a person often acquires cancer earlier than the norm for that type of cancer by accumulating mutations more rapidly.  All the cells of a tissue with the gene that checks replication, for example that has been disabled are accumulating mutations in the DNA at an accelerated rate.  If however, instead of being inherited the P53 has through random mutation has been disable, only the progeny of that one cell are accumulating mutations at an accelerated rate, including those to the various oncogenes[vii]   This later scenario occurs in 90% of the cancers—inheritance accounts for under 10% of all cancers.

THERE ARE A LARGE NUMBER OF GENES WHICH CAN PLAY A ROLE IN THE PORDUCTION OF A CACEROUS CELL LINE. Scientists have identified over 100 genes that are involved in the twelve above processes.  Since a gene occurs on both strands of a chromosome, one inherited from the mother, the other from the father, normally the gene in each strand must be altered by mutation. In some cancers however, the two alleles have not been disabled, but rather their production reduced.   The gross errors in chromosome replication (aneuploidy), such as translocation, can alter the production of an oncogene.  Often for a tumor, the cells are not just aneuploidy, but also unstable, changing every few generations.  In about half of the aneuploidy cells, the mechanism involves the formation of spindles during mitosis.[viii]  Cell biology is complex, and as I pointed out over a decade ago and others still affirm, “each tumor is unique.”[ix] 

RATE OF  MUTATION:  There are 4 scenarios for speeding up the rate of mutations.  One is a mutation in a single cell that disables one of the systems that checks to see that during mitosis the newly formed mRNA and the DNA are as proscribed by the parent strand of DNA.  With this system disabled, the rate of mutations (imperfect copies of the DNA or RNA) is increased that cell several fold.  Second, this disabling of all the cells due to an inherited mutation in that system.  This occurs in only a couple of percent, though such people typically run around a 90% risk of developing cancer in the affected tissue.  A third one is through a cancer-causing retrovirus that has “hijacked” proto-oncogenes from their host’s genome, mutating them in the process to make malfunctioning versions.   “Only 15 percent of human cancers are caused by genes introduced by viruses” (Bailey 137).  The fourth is environmental factors, namely mutagenic substances and radiation including sunshine.  The primary environmental one is in air filtered through tobacco.  Consistent with other later studies, Ravenholt (1983) found that there were 450,000 premature deaths caused by tobacco, including 50,000 from second-hand smoke—a figure that has remained constant over 3 decades.   

CARCINOGENS ARE A CASUAL FACTOR THROUGH NATURAL SELECTION:  A particular mutation or set of mutations will confer upon an exposed tissue survival advantage.[x]  Cancerous cell mired in tobacco tars have a survival advantage over normal tissue.  Even when survival is not an issue, the cancerous cells have a reproductive advantage, and thus crowd out or replace normal tissue.  In fact, which aneuploid cells survive is a result of natural selection, since most of them when formed anew are still born or abnormally slow growing. A rare success case gives that cell line a selective advantage.  Gene mutations and chromosome abnormalities, in rare instances, confer numerical advantage to a cell line.[xi] 

NATURAL SELECTION PLAYS A ROLE IN RESISTANCE TO CHEMOTHERAPY:  A cell line with the ability to undergo genetic alterations at high rate can become resistant to chemotherapy.  Thus initial success evaporates when one of the cancerous cells undergoes a mutation that makes it, and thus the new cell line resistant to a particular chemotherapy.   

FOUR STAGES OF CANCER:  Four things affect cancer survival.  One is the stage of its development.  Second is the primary tissue in which it evolved.  Each tissue has its own prognosis.  Pancreas has 3 tissues; however, the prognosis is equally dismal for each tissue—the 5-year survival rate is under 2%.  The third factor is where the mutations have occurred on the sequences of codons[xii] that make up a gene, and also what letter of the codon has been substituted; or if there was aneuploidy, where that has occurred.  Not all mutations of the same gene are equal.  So too does the combination of mutations giving rise to a particular cancer affect the prognosis, including both the body’s immune response and the effects of chemo and other therapies.  These differences create the great variation of responses to treatment for a cancer in the same stage (1 through 4) of the same primary tissue in different patients.  The fourth factor is the cancerous tissues ability to becoming resistant to chemotherapy.  If the tissue posses a process which accelerates genetic diversity, such as the defective spindle formation during mitosis (described earlier), then the chances of the cancer becoming resistant to chemotherapy are greater than a similar type of cancer without the defective mitosis.  A cancer will be in remission, often for years, and then suddenly again prove life threatening, and the previous successful chemotherapy proves ineffective.  Four factors thus are relevant in making a prediction as to prognosis. 

WHY TREATMENT WITH CHEMOTHERAPY IS UNCERTAIN:  The fundamental cause for the difficulty in devising effective noninvasive (radiation, heat, excision, and like are all invasive and directed at the tumor) methods of treatment for cancer, viz., chemotherapy, is that of finding chemicals that are sufficiently selective as to primarily target the cancer cells and disrupts their growth while not disrupting normal cells and bodily functions.  The difficult arises because cancer cells are genetically nearly identical to normal cells.  In most cases chemotherapy does not eliminate cancer, but rather produces remission and thus prolongs life. 

Chemotherapy is used is most commonly used following invasive treatments even when there is no clear evidence of metastasis.  Studies have shown an improved survival rate for those who receive chemotherapy as an adjunct to excision for nearly all cancers that have progressed beyond stage 1. 

The three leading avoidable causes of cancer are tobacco smoke, obesity, and high-fat diet (most carcinogens are fat soluble).  Cancer is a crapshoot; however, risk goes up with age.  A 70-year old is 100 times as likely to be diagnosed with a malignancy as a 19-year old (Gibbs 58).  There are 10 million billion cells that have cooperated in the course of an 80-year life span.  Considering this number of cell, only about 40% of the population will develop a cancer serious enough to result in medical intervention.  Nature has endowed us with a set of quite effective safeguards against cancer.