Telomolecular is developing a pipeline of cutting edge technologies that may effectively address many forms of cancer including:

1. hTert mediated putative therapy (HMPT)
2. Reactivation of tumor suppressor genes (RTSG)
3. Reactivation of DNA damage checkpoint control (RDDCC)

Mediated Putative Therapy

Telomere therapy has putative potential as a powerful preventative medicine in the treatment of cancer. The Corporation’s innovative strategy therapeutically lengthens chromosomal telomeres by delivering raw enzymes in a way that does not alter genes or cause cell immortalization. A non-immortalizing therapy administed before cell's enter cell crisis may greatly offset cancer formation. The statistically most relevant cause of cancer is critical telomere shortening.

The Telomolecular strategy

1. offsets cancer by preventing "cell crisis" and the development of "premalignant" tissues
2. does not cause "overproliferation" seen in immortalized cells
3. does not "immortalize" cells
4. stabilizes the genome and improves DNA damage checkpoint control and tumor suppression.

Telomeres and cancer are interdependent subjects. More than 90% of all cancer is caused by critical telomere shortening, for example, in 97% of premalignant endothelial lesions critical telomere shortening is observed (Meeker, John Hopkins University 2005). These "destabilized" cells have a tendency to transform as a result of end-to-end chromosomal fusions or as a result of a generally high metastatic potential due to down regulated protein production. After the accumulation of critical errors a cell may immortalize. Immortal cells express high levels of telomerase, which stimulates cell proliferation and permits cancer cells to grow without limitation. When p53 DNA damage checkpoint control and pRB tumor suppressor pathways have been deactivated, immortalization in normal somatic cells is dangerous. Paradoxically, p53 and p16 pathways do not tend to inactivate when chromosomal telomeres are healthy, even if immortalized. In the laboratory, immortalization of normal somatic cells does not lead to the development of cancer and generally prohibits "cell crisis", a fundamental process that is required in the development of most cancer. In hundreds of parallel experiments, when immortalized cell lines are pushed beyond their traditional replicative capacities cancer has never been observed.

It may be possible with traditional technologies (though not very comprehensively) to deliver viruses that alter genes and cause them to immortalize, however this tactic would enable cancer in exotic circumstances, particularly if an oncolytic virus like SV40 and an oncygen like Ras are simultaneously present. Telomolecular's therapeutic strategy is based largely on addressing this risk. Instead of immortalizing the cell through gene modification in a gene therapy we emphasize the delivery of a therapeutic dose of the active TERT enzyme. In this way cells avoid cell crisis but viruses and carcinogens are unable to benefit from immortalization as an easier means of circumventing cell arrest. Management believes that this strategy will greatly inhibit the formation of cancer and has putative potential as a preventative medicine.

"It appears that the telomere shortening frequently observed in large advanced tumors has already occurred before it can be detected by standard diagnostic tools, when cellular changes characteristic of early precancer can only be seen through a microscope by a pathologist," says Angelo M. De Marzo, M.D., Ph.D., senior author of the study and associate professor of urology, pathology and oncology at Johns Hopkins. "Therefore, intervention strategies aimed at preventing, or even reversing, telomere shortening may be effective in lowering cancer incidence. And assessing telomere length may provide a new direction for cancer prevention studies, and lead to improved early diagnosis of precancerous lesions."

In addition to potential preventative therapies that may offset or prevent cancer, Telomolecular is focused on the discovery of inducible genes and enzymes (and the acquisition of licenses) that may activate p53 DNA damage checkpoint control, pRB tumor suppressor, and other tumor suppressors. Inactivation of the p53 tumor suppressor protein, by mutation or by viruses, has been identified in over one-half of all human tumors. The inactivated protein usually has reduced DNA-binding capacity, which renders it ineffective in regulating cell division and cell growth. Delivery of the p53 gene to tumor cells has led to the elimination of the tumor in both animal models and some early clinical studies. The retinoblastoma protein (pRb)/cyclin/cyclin-dependent kinase (Cdk)/p16 tumor-suppressor pathway participates in the regulation of cellular proliferation and undergoes mutational or epigenetic inactivation in essentially 100% of selected human malignancies. Since this pathway is frequently altered by inactivation of either the RB gene or the upstream Cdk4/6-inhibitor gene, Cdkn2a/p16ink4a, it is commonly referred to as the RB/p16 tumor-suppressor pathway. Reactivating this pathway appears to be a promising approach in delimiting human cancers.

This technique promises to form the basis of new cancer treatments based on protein therapy. These treatments will use tumor suppressor proteins to hault cancer growth. Currently, biological treatments have been limited to those that act outside the cell. Significant technical barriers, such as engineering a vector that could cross the cell membrane efficiently, have hampered development of strategies that would allow researchers to deliver proteins to intracellular locations.