Cancer science, hypes, cures and hopes

C.D. Fermin, T. Samuel, T. Yehualaeshet, L. Billups

Cancer is difficult to conquer in all living systems.   Despite decades of work at the clinical and the research level, a cure for certain types of cancer is still years away and cancer incidence continues to grow (http://apps.nccd.cdc.gov/uscs/Table.aspx?Group=TableAll&Year=2003&Display=n) .   It is known, however, that most cancers arise by an uncontrollable replication of cells that lose their ability to halt the normal management of their genomic materials. Cancer cells continue to divide where other cells will wait for a specific signal to continue dividing.   In addition cancer cells, ignore the stop and go signals that maintain a proper balance in tissue growth, but also recruit adjacent blood vessel (angiogenesis) to bring nutrients into the area.   In a very provocative review by Wyatt Gibbs (Gibbs 2003) , "six diabolical super powers of cancer are given:"

1) Cancer cells can counterfeit their own pro-growth message.  

2) Malignant cells ignore commands given by neighboring cells.  

3) Cancer cells bypass the suicide mechanisms when something goes wrong.

4) Cancer cells can corrupt nearby blood vessels to bring needed nutrients to develop into growing masses.

5) Cancer cells work around control systems such as telomeres to enhance their reproductive immortality.

6) Cancer cells disable cellular circuitry that allows them to become immortal.

Table showing Major Types of Cancer & Therapies

Death Rates are per 100,000 persons and are age-adjusted to the 2000 U.S. standard population (Source: CDC ) .

Age-adjusted Rates per 100,000?

Race and Ethnicity

Incidence Rate

All Races     64.9

White          67.3

Black          56.5

Asian/Pacific Islanders (API) ?*

American Indian/Alaska Natives (AI/AN) ? *

Hispanic ??             *

Changes to cell microenvironments and/or trafficking may contribute to corruption, instability and alterations of the DNA in such a way that misassortment of chromosomes eventually lead to derangement of the cells functioning.   Such an idea is corroborated by colorectal cancer, in which a gain of chromosomes 7, 8, 13, or 20 and the loss of chromosome 18 occurs (Sidransky 1996) .   Unfortunately, there is no known effective mean to selectively kill cells that have abnormal chromosomes.

While the role of mutations and/or chromosome re-arrangement in the production of tumor is undisputed, the effect of factors that lead to the development of new blood vessels (angiogenesis) become a very important variable in cancer development and management.   This is because without nutrients, the tumor cannot survive.   Unfortunately, tumor blood vessels and vessels of normal healthy tissues required for homoestasis of the cells are difficult to separate.   In fact, such a difficulty (lack of demarcation of tumor border) contributes to the re-emergence of tumors after surgical excision.   Conversely, methods to try to control angiogenesis of tumor will inevitably affect the blood vessel needed for normal function of the body and consequently have negative side effects.   Nonetheless, in areas where blood vessels can be isolated, such as in the fast-growing vascular area behind the photoreceptor of the retina, a combination of chemical, physical, and biological approach may lead to the destruction of specific groups of blood vessels, as is the case in macular degeneration.   The outcome of nanotechnology may come to the rescue of cancer therapy by permitting targeting the tumor microenvironment.   It is possible that pigment such as porphyrins that are currently used to activate oxygen radicals that aide in the destruction tumor cells and fast growing blood vessels may one day lead to more specific eradication of certain tumor by and/or with specific markers (Lane 2003) .  

Multiple cooperating mutations capable of deregulating various signaling pathways contribute to cellular derangement that lead to cancer (Du et al. 2005) .   Insertional mutagenisis of cooperating cancer genes by a defective oncogenic retrovirus may provide new hopes for identifying gene changes that may trigger cancer for eventual development of new therapies (Yi et al. 2006; Yi et al. 2007) .   Current studies with replication competent retrovirus offer additional hopes.   In a recent study by (Hiraoka et al. 2007) , a suicide gene was delivered by replication competent retrovirus vectors directly into the portal circulation with an effective reduction of liver tumors without spread to the adjacent normal liver parenchyma.   More recently to overcome problems associated with the full replication defective retrovirus vectors (Qiao et al. 2006) developed a semi-replication competent retrovirus.   The authors were able to induce tumor killing by cytotoxicity of the intended virus target through the semi-replication competent retrovirus when followed by gancyclovir application to tumors grown in nude mice.   Another promising technique is silencing of oncogenes by retrovirus mediated siRNA delivery.   (Yang et al. 2003) used an ovarian surface epithelial cell line whose tumorigenecity depends on the H-ras gene.   Through a retrovirus mediated siRNA against H-ras theywere able to increase the rate of apoptosis of the cells, arrest proliferation, and block additional transformation, reducing tumor growth in nude mice (Wang-Johanning et al. 2007) .

One of the fastest growing molecular hopes to cancer eradication is virus research that offers hope for viral therapy to human cancer cells.   Many researchers are investigating the potential of herpes simplex virus, parvovirus, baculovirus, retrovirus and others ( see http://www.virology.net/garryfavwebindex.html ) in understanding the genetic switches required for controlling the proliferation of tumor cells.   Adenovirus tools are used extensively because the biology of this virus is very well understood and they are prevalent in flu-like infections and colds that most humans acquire one or twice a year.   Viruses are easily manipulated to deliver specific molecular signatures to infected cells.   The so-called therapeutic viruses can make cells uniquely susceptible to chemotherapy or phototherapy for destruction of target tissues.  

Clearly, understanding the origin and progression of cancer requires technologies that we have not yet developed. There is hope in the manipulation of the genome of the tumor cells and also in the re-designing and re-engineering of both adenoviruses and retroviruses capable of delivering cargos into the cells that will make them more susceptible to chemotherapy, photodynamics and other methods.

Age-Adjusted Invasive Cancer Incidence Rates for the 10 Primary Sites with the Highest Rates within State- and Sex-Specific Categories ( Source: CDC ).

Rates are per 100,000 persons and are age-adjusted to the 2000 U.S. standard population (19 age groups - Census P25-1130).   Rates are per 100,000 persons and are age-adjusted to the 2000 U.S. standard population.

Despite advances in cancer research, it is still undisputed that chemical (Cancer 1996) , dietary and environmental factors play a very important role in the development of cancer.   For instance, (Briskey et al. 2000) reported a prevalence of bad nutrition with increase in obesity, lack of activity and poor dietary habits exacerbate inherited conditions that may predispose patients to develop cancer (Sidransky 1996) .  

Genetic and acquired influences probably interact in various ways that still need further investigation (Willett et al. 1996) .   A good example is the use of vitamins and other factors (Carper 1993; Reavley 1998) .   Folate often reduces hemocysteine levels and a fortification of this component in the diet has greater impact in elderly where levels of these factors decrease with age.   It is also evident that diets low in saturated fats such as most Mediterranean cuisines have beneficial health effects and may aid in cancer prevention (Bogani et al. 2007; de Lorgeril et al. 2007; Rubba et al. 2007; Zeghichi-Hamri et al. 2007) .  

Several disorders related to folate and cobalamin deficiency (Carbone et al. 1994) are now under investigation because there could be an interplay between the environmental factors and genetic predisposition that effect progression or inhibition the tumor growth of different origins.   Chemoprevention (Serrano et al. 2004) also offers help as micronutrients of a good diet have been associated with improvement of health conditions and reduction of certain maladies.  

Scientific evidence is slowly corroborating anecdotal accounts for the benefits of certain natural foods and drinks.   For instance (McCarty et al. 2005) reported that the angiostatic activity of orally administered green tea is most likely due to an inhibition of the vascular endothelial growth factor (VEGF).   In 1996, (Trichopoulos et al. 1996) emphasized " that the role of vegetables and fruits in cancer prevention is based on overwhelming epidemiological data for which the precise biological mechanisms are not fully understood ."   Thus, we need to delve deeper into the biological drivers of the disease emphasizing the benefits of measures that aid in prevention. These researchers further concluded over 10 years ago that if "one eats right, one can live longer" and that a reduction in saturated fats will have a tremendous impact on prostate and colorectal cancer.   Yet, we find ourselves in the same boat, rowing very slowly toward the finish line of a cancer cure.   The above workers further pointed out that most of the differences in cancer incidences between races can be attributed to socio-economic factors, some of which include diet and environmental carcinogens.   And while it is understandable that some differences may have genetic basis, genetic liability remains high between races.   Thus, the "majority of the differences between Black, White and Asian can probably be traced to diet and environmental factors and other socio-economical variables."   Over a decade ago, these investigators emphasized that Japanese women in Japan had 25 percent of the risk for breast cancer that a white woman had in the United States.   However third generation Japanese American women contract cancer almost as frequent as other American women do, corroborating the presumption that changes in the environment, diet and behavior contribute to the development of some of these malignancies.

Table showing Potential Cancer Triggers and Preventive Measures

(Willett et al. 1996) also pointed out that diet should be high in vegetables, fruits and legumes and low in red meat, saturated fats, salt and sugar and that carbohydrates should be consumed as whole grains as opposed to white grains, which are found commonly in cheap breads and snacks.   The diets that are currently advertised in most media to the most vulnerable, are in complete contrast to those recommendations .   The recommendations of the report in 1996 was that "any one can reduce his or her chance of being afflicted with cancer by following some sensible preventive guidelines:   eat plenty of vegetables and fruits; exercise regularly and avoid weight gain; and, avoid tobacco smoke, animal fat, red meat, excessive alcohol consumption, the mid-day sun, risky sexual practices, and known carcinogens in the environment or workplace."   Yet despite 10 years of research since those recommendations were published and much political haggling we still are unable to convince our citizens of these simple recommendations.   Worse, we are unable to implement changes in school nutritional programs that will ensure good adult dietary habits in our most precious investments of the future: children.

In a report by (Greenwald 1996) , Michael Sporn stated, " Obsession with curing advanced diseases has blinded cancer researchers to the promise of prevention ."   Indeed, healthy diet, exercise and avoidance of risk factors mentioned above go a long way to help those who cannot afford medical care.   The effect of chemicals found in plants (Lewis et al. 1977; Stwart 1979) is now undisputed and good examples are such chemicals as tamoxifen (bark of a tree), and others such as dithiolthiones, groups of chemopreventive agents found in cruciferous vegetables such as broccoli, cauliflower and cabbage.   The challenge for the new wave of scientists is to determine how these chemicals found in these plants, vegetables, fruits and roots, may cooperate with genes and metabolic reactions in the cells to either enhance or reduce the potential effect that they have on signal transduction and biological processes that may facilitate tumor development.   It is obvious that many of the cancers arising today are exacerbated by the lifestyle that humans have chosen, their inability to follow meaningful counseling, and/or inadequate healthcare.  

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