Cancer theories

S. Epstein, and J. Swartz, The fallacies of lifestyle cancer theories. Nature, 289 (January), 1981. 

The main point of contention was whether the toxicological profile should discuss the xenoestrogen/breast cancer theory in the first place. Consistent with their earlier debates, some panelists thought the theory should be omitted from the profile, but others disagreed and thought the profile should briefly mention the theory, along with its uncertainties. 

Figure 5.9. The Cori cycle. Note that muscle and other tissues can produce excessive lactic acid in early cancer. Some lactate ionizes to H ion and thus lowers local pH. These acid effects are thought to disturb cell-to-cell interactions by ceUnlar water and pH imbalances with chromatin/DNA rearrangements and hence is proposed to initiate neoplastic environments according to the Warburg cancer theory. The Cori cycle repeats many times in advancing cancer and because of the net loss of energy by 2 ATP - 6 ATP = -4 ATPs per each Cori cycle, there is loss in the ability maintain tissne. Hence, there is a wasting of tissne over time. Cachexia is seen in a high percentage of terminal cancer patients.

In sum, the viral or microbial theories or mechanisms of cancer formation and its cure seem for the most part plausible. If these theories can be tied in with the cancer-forming consequences, say, of radiation and chemicals — and they seemingly can — and with the anticancer effects of other agents, in particular plants and herbs, this would round out the picture. As such, it will furnish a way to unify cancer theory at the most elementary level. 

Fonorow, O.R. 2004. The Cure for Cancer Theory, History and Treatment. Townsend Letter for Doctors and Patients, no. 251 (June) 118-120. 

ITowever, most normal somatic cells lack telomerase. Consequently, upon every cycle of cell division when the cell replicates its DNA, about 50-nucleotide portions are lost from the end of each telomere. Thus, over time, the telomeres of somatic cells in animals become shorter and shorter, eventually leading to chromosome instability and cell death. This phenomenon has led some scientists to espouse a telomere theory of aging that implicates telomere shortening as the principal factor in cell, tissue, and even organism aging. Interestingly, cancer cells appear immortal because they continue to reproduce indefinitely. A survey of 20 different tumor types by Geron Corporation of Menlo Park, California, revealed that all contained telomerase activity. 

This interceptor theory does not seem to be the only protective mechanism in operation. Inhibition of cytochrome P450 enzymes related to the bioactivation of mutagens and toxic radical scavenger activities have been proposed to integrate the different modes of action. Other investigations have reported the involvement of chlorophyUin in inducing apoptosis in human colon cells, which may be important in limiting cancer cell invasion and metastasis. ... 

Breast cancer was not increased in the ERT arm of the WHI, and in fact, the risk was non-significantly lower in the ERT group than in the placebo group.21 These conflicting data point to a possible link of progestin with breast cancer risk however, this theory needs to be studied further. 

ASHP Technical Assistance Bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990 47 1033-1049. Blagosklonny MV. Molecular theory of cancer. Cancer Biol Ther 2005 4(6) 621-627. 

The principal research goal of our project is to test the linear-no threshold dose-response theory for radon-induced lung cancer. This... 

M = total mortality rate from lung cancer Mr = lung cancer mortality rate due to radon Mn = lung cancer mortality rate due to non-radon causes including smoking and all other factors, known or unknown r = average radon level in a county Then, from the linear-no threshold theory,... 

Eq.(l) is not valid, which means that the linear-no threshold theory fails, grossly over-predicting the cancer risk at low doses. 

Marshall, J.H., and P.G.A. Groer, A Theory of the Induction of Bone Cancer by Alpha Radiation, Radiation Research 71 149-192 (1977). 

Portier, C. and Hoel, D. (1984). Type I error of trend tests in proportions and the design of cancer screens. Comm. Stat. Theory Meth. A13 1-14. 

As indicated above in the section on "Genotoxic Effects", it is likely that mirex and chlordecone are tumor promoters and not tumor initiators. Initiators irreversibly alter DNA by a mutation, chromosomal aberration, or other alteration. Promoters act by facilitating the proliferation of previously initiated preneoplastic cells. One of the mechanisms for promotion is believed to involve suppression of inhibitory proliferative control through inhibition of gap-junctional-mediated intercellular communication as well as enzyme induction (Trosko et al. 1983). The results of studies to evaluate the promotional activity potential of mirex in mice indicate that mirex is a mouse skin cancer promoter but exerts this toxicity through a hitherto unknown mechanism that is different from that of phorbol esters, such as TPA (Meyer et al. 1993, 1994 Moser et al. 1992, 1993). Unlike initiation, promotion is a reversible process to a point. This implies, at least in theory, that there may be justification for setting NOAELs for promoters. 

Inverse Relationship between Protease Inhibitors and Metastatic Ability. All proteases, apart from possibly CD, appear to be controlled by endogenous inhibitors. In theory, therefore, the ability of malignant cells to produce metastasis could depend not only on the levels of the specific protease, but also on the concentration of relevant endogenous inhibitors. Thus, the presence of high levels of protease inhibitors might inhibit metastasis, while low levels of inhibitors might enhance metastasis. An inverse relationship between a number of specific inhibitors and metastatic potential has now been shown. Some examples of this type of relationship include TIMP-1 in Swiss 3T3 cells (K4), cysteine protease inhibitors in mouse melanoma cells (R6), and an alpha-1-proteinase inhibitor in rat mammary carcinomas (N2). Furthermore, a newly described serine protease inhibitor, known as maspin, was found to be expressed less frequently in advanced human breast cancers compared with early cancers (Z2). 

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