Cancer and Stem Cells

There is a growing body of scientific evidence that many forms of cancers may arise as a result of dysfunctional stem cells residing in normal tissues. At the 96th Annual Meeting of the American Association for Cancer Research held in Anaheim, California in April 2005, cancer scientists reported the relationship between stem cells and cancer cells. With the ability to grow stem cells from adult tissues, cancer researchers are finding many similarities and parallels with regard to the behavior and phenotypic expression of adult stem cells and cancer cells grown in primary tissue cultures. Moraga's BLSC could be the ideal cell for studying cancer as well as for developing novel anti-cancer drugs. Using pluripotent adult-derived stem cells, it was discovered that many of the genes that were once thought to be cancer genes (oncogenes) may turn out to be stem cell genes that are not turned off (down-regulated) during commitment to a particular tissue lineage as they begin to differentiate and mature.

Cancer is a term for diseases in which abnormal cells divide without control. The word cancer originated from the Latin word for crab, because the swollen veins around a surface tumor appeared like the legs of a crab. Cancer is a popular generic term for the medical terminology of neoplasm. This term neoplasm or neoplasia comes from the Greek, meaning new formation. Cancer cells can invade nearby tissues and spread to other parts of the body either by the bloodstream, lymphatic system, or direct spread. This process is called metastasis. Cancer cells also do not undergo programmed cell death. This process is called apoptosis. Similar to BLSCs and embryonic stem cells, cancer cells have unlimited proliferative potential when cultivated in cell culture.

Cancer is thought to be a disease caused by genetic aberrations by either mutations or environmental insults, which can lead to fragmentation of a cell's DNA. It is typically thought that a series of several mutations are required before a normal cell becomes a cancer cell ("multi-hit theory"). The transformation process from normal to cancer cells seems to involve both oncogenes and tumor suppressor genes. Oncogenes promote cancer when "switched on", whereas tumor suppressor genes prevent cancer unless they are "switched off."

Cancer biologists have long ago postulated that abnormal genetic events cause normal cells to undergo unregulated cell division by their inability to control oncogene activity and inactivation of tumor suppressor genes. Turning "on" or "off" these genes can occur either through direct mutation of the genes or by inhibiting the activity of regulatory cellular proteins involved in cell division. In a targeted approach to prevent unregulated cell division, anti-cancer therapeutics are being developed that target intracellular proteins involved in the intracellular signaling pathways that can drive the cancer cell to apoptosis and senescence.

Another approach is to develop drugs that block cell division during mitosis by preventing cancer cells to progress through the cell cycle. Preventing cells to divide during mitosis will also lead to apoptosis and cell death. In the last few years, monoclonal antibodies have used this targeted approach to treat cancer patients and they have become blockbuster drugs. Drugs such as Genentech's Herceptin (HER-2neu), Biogen-Idec's Rituxan (CD22), and ImClone's Erbitux (anti-EGF receptor) are monoclonal antibodies that drive cancer cells to apoptosis by targeting the cancer cells surface receptors which interfere with the signal transduction pathways involved in cellular proliferation.

Moraga's BLSCs can be used as a research reagent to identify new targets for developing anti-cancer therapeutics. Compared to the behavior of cancer cell grown in cell cultures, the Company founders have discovered that its BLSCs also exhibit similar characteristics. The BLSCs demonstrate the following characteristics:

Due to the similarities between cancer cells and the BLSCs, Moraga's scientific founders have a different perspective on the etiology of cancer. The Company has hypothesized that cancer is a disease arising from dysfunctional stem cells. These hyperproliferating cells are a result of mutational events, which block the maturation and differentiation of stem cells from becoming functional cells of the body's tissues. Additionally, the Company believes that terminally differentiated cells that make up an organ or tissue cannot dedifferentiate into a more primitive cancer cell; irrespective of genetic instability created through mutations.

Cancer cells seem to be stuck in their stem cell state after being activated ("awakened") from their normal quiescent state. Under normal conditions, the body's stem cells undergo a highly regulated process of proliferation to replenish cells within tissues that have senesced due to normal "wear and tear." This regulated process of tissue renewal is called homeostasis. As a result of tissue damage due to injury or disease, however, the stem cells are activated to a hyperproliferative state as a response to repair the damaged tissue or organ. Stem cells have also been demonstrated to migrate toward an injury site and begin to differentiate as a mechanism in supporting acute tissue repair.

If cancer is assumed to be an uncontrolled stem cell disease, one can conclude from this hypothesis that an obvious treatment regimen would be to find agents that cause cancer cells to re-engage in the pathway leading to terminal differentiation of the blocked cancer cell. Using a cell-based, high throughput, screening platform of BLSCs, the Company believes its reagents can prove to be an invaluable tool in the war to cure cancer. Drugs discovered by this approach may prove to be more efficacious because of its more targeted approach to drive cancer cells to apoptosis. This therapeutic regimen may prove to be much less toxic because normal cells within the body are already differentiated and therefore unaffected by this novel therapeutic approach.