Due to the wide genomic and etiological diversity of cancers, a single broad-spectrum anticancer therapy does not yet exist. Moreover, genetic mutation often occurs during conventional cancer therapy, thereby leading to the formation of drug-resistant cancers. That, combined with the fact that there are very few if any reliable methods for predicting the therapeutic response of a particular cancer by a particular compound, has led the pharmaceutical industry to develop therapies relying upon very targeted molecular mechanisms of action and to try treat cancer with compounds or mixtures of compounds while having little to no confidence a priori of the ultimate efficacy of a particular therapy against a particular cancer.
Phoenix has taken a different approach. First, our products have been developed to exploit multiple mechanisms of action. Second, anticancer therapy with our products relies upon a prognostic assay, whereby a clinician will be able to predict the potential for successful treatment prior to initiation of treatment. The result is that the potential for effective treatment is high, and the potential for development of drug-resistant cancer is low.
Our oleandrin-containing products are selectively toxic to human malignant cells but not to human normal cells. Oleandrin binds to selected specific cellular tumor cell targets causing cellular downstream changes to certain signal transduction pathways, but not to healthy cells.
The selective cytotoxicity against cancer cells is primarily due to the increased expression of the α3-isoform of the Na,K-ATPase enzyme in malignant cells. For example, as colon cells undergo a change from a normal phenotype to a malignant phenotype, they increase expression of the α3 subunit. This then makes the malignant cells unique targets our products while sparing normal cells.
Our finding of the increased expression of the α3 subunit (in cancer cells) as compared to the α1 subunit (in healthy cells) is in fact the basis for the company’s above-mentioned prognostic assay.
The promise of PBI-05204 and ANVIRZEL®, both of which have undergone human clinical trials, appears great. Both products have demonstrated activity against difficult to treat human cancers such as melanoma, prostate, and breast cancers as well as certain hematologic malignancies.
Further Information: See “Product Development” or “Contacts”.