A Possible Explanation of Multidrug Resistant Cancer: Low Dehydroepiandrosterone (DHEA) and High Prolactin

Copyright 2016, James Michael Howard, Fayetteville, Arkansas, U.S.A.

It is my hypothesis that low dehydroepiandrosterone (DHEA) can initiate cancer by reducing cellular adhesion. Also, it is my hypothesis that high levels of DHEA affect genes of cell division and low levels affect gene activation of the differentiated state of DNA. (When DHEA is high, cell division is abundant but is counteracted by low DHEA and genes of differentiation.) That is, high DHEA activates genes of cellular division while lower DHEA activates genes of more advanced differentiation. Therefore, if cellular adhesion is reduced, more DHEA may enter a cell thereby activating genes of cell division usually not active in cells which are part of a tissue (oncogenes). Reduced DHEA within an organism may appear as increased DHEA to a cell which has increased its surface area. This combination of "increased" DHEA within a cell which contains an expressible gene of cell division (oncogene) may cause cancer.

In 1994, I first suggested that low DHEA is directly involved in initiation of oncogenes: "An Explanation of Cancer and the Increase in Cancer: High Testosterone, Low DHEA and Breast Cancer," at: http://anthropogeny.com/An%20Explanation%20of%20Cancer%20and%20the%20Increase%20in%20Cancer.htm which appeared first in publication: Annals of Internal Medicine 2005; 142: 471-472 .

The phenomenon / phenomena of multidrug resistance (MDR) is a significant problem. As I have pursued my explanation of the interaction of DHEA and testosterone in human evolution, I often confront this issue. Because I think cancer, once initiated, also depends on a supply of DHEA, as all tissues do, I looked for a reduction in available DHEA caused by anticancer therapies. (“Lung Cancer Surgery, Radiation Therapy, and DHEA,” at: http://anthropogeny.com/Lung%20Cancer%20Surgery%20and%20Radiation%20Therapy.htm ) While it is circuitous and not strong, a case may be made that some anticancer drugs may actually produce anticancer effects by reducing available DHEA for cancer growth. (Since I think all tissues rely on DHEA, one may see that this explains the negative effects of some anticancer drugs. (Testosterone reduces DHEA levels. Testosterone is highest in humans compared to the Great Apes; cancer is far higher in humans than the Great Apes. It is my hypothesis of 1994 that increased testosterone increases breast cancer, as well as other cancers, (International Journal of Cancer 2005; 115: 497). This also explains why breast cancer is increasing; it is my hypothesis that women of higher testosterone are increasing in percentage within the population with time. This effect involves testosterone's effects on levels of dehydroepiandrosterone (DHEA). That is, testosterone reduces overall availability of DHEA.)

Since I was not satisfied with the available connection of anticancer drugs and DHEA, I thought to examine a possible connection of prolactin with MDR. Prolactin (PRL) is a direct and specific stimulator of DHEA. A case may be made that PRL and DHEA act cyclically to maintain DHEA levels; when PRL is high, DHEA is low.

A number of reports in the literature support high levels of PRL with multidrug resistance. High PRL should indicate that DHEA is low.

As stated above, I think low DHEA allows initiation of cancers by decreasing cell adhesion. This allows initiation of genes of cell division (oncogenes). Anticancer drugs, I suggest, exert their effects by reducing DHEA. This is supported in the association of high PRL in drug resistance in this manner: As cancer cells are exposed to reduced DHEA caused by chemotherapy, this kills some cells. However, not all cells are killed and these demonstrate multidrug resistance and the host produces increased PRL in an attempt to increase DHEA. I suggest this is caused by subsequent initiation of cancer in cells that are exposed to reduced DHEA as other cells die. It still is low DHEA which initiates cancer formation and anti-DHEA therapy then starts cancer in cells that are exposed to reduced DHEA and cell adhesion. High prolactin is a sign of low DHEA. (Cancer is initiated more often in the elderly because of low DHEA but these cancers grow less rapidly because of the natural decline of DHEA of old age.)

The phenomenon of “drug holidays” may actually be explained by the foregoing. Drug holidays may allow a “rebound” of DHEA which then may re-induce vulnerability of rapid cancer growth, again, to DHEA reductions.