PG500 Series in Cancer Therapy - Essay Example

The paper “The PG500 Series in Cancer Therapy - How the Technology Works" is a forceful example of a term paper on health sciences & medicine. With increasing evidence that tumors are dependent on the process of angiogenesis for continued growth, inhibition of this process is now regarded as a vital cancer therapeutic strategy. Heparan sulfate in the extra-cellular matrix plays a critical role in regulating the process of angiogenesis, thus regulating the progression of tumors and subsequent metastasis, all of which are key steps in the progression of cancer (Dredge et al, 2010).

Heparan sulfate has particular binding sites for tumor-related growth factors, enzymes, molecules, and their receptors, which are deactivated once they are bound on these sites. Thus, heparan sulfate mimetics can be used as potent blockers of these binding sites, thus inhibiting crucial processes in tumor progression. PG500 series compounds are potent heparan sulfate mimetics that interfere with the process of angiogenesis through inhibition of fibroblast growth factor-2, fibroblast growth factor-1, and vascular endothelial growth factor (Dredge et al, 2010).

  Moreover, the PG500 series compounds block the process of metastasis by inhibiting the activity of heparanase enzyme, which is involved in the degradation of polymeric heparan sulfate in the extra-cellular and intra-cellular matrices (Dredge et al, 2010). Heparanase has also been implicated in the facilitation of tumor lymphangiogenesis. This is the process through which additional lymphatic vessels are formed around tumor cells, which is facilitated by heparanase through induction of VEGF-C, as well as acting as a signaling molecule for the induction of VEGF.

Therefore, enhanced expression of this enzyme by tumor cells is directly correlated with tumor vascularity and metastasis, while its protein reduces the survival rates of patients following operation (Dredge et al, 2010). Thus, by blocking the activity of this enzyme using PG500 series compounds, the growth, vascularization, and metastasis of tumor cells in humans can be controlled. How It Was Applied To Solve a Particular Problem The PG500 series compounds were used to study whether they could improve biological activity against tumor growth and cancer development in comparison to the older heparin or PI-88 compounds that possessed anti-coagulant activity, limiting their effectiveness.

It was found to have a dual-action mode, unlike the latter compounds, due to its potent inhibition of angiogenesis and heparanase enzyme activity (Dredge et al, 2010). In this study, the three compounds were investigated for their affinity to bind VEGF, FGF-2, and FGF-1 compounds, as well as for their heparanase inhibitory activity. It was found that PG500 series compounds PG562, PG545, PG537, and PG536 had higher inhibitory activity for the above growth factors compared to PI-88, as well as earlier PG500 compounds like PG518 and PG517.

In an angiogenesis assay to test anti-angiogenetic properties, it was found that PG545, PG536, and PG546 were the most potent inhibitors of angiogenesis after daily administration of 10 µM for a period of 6-8 days (Dredge et al, 2010). In addition, these compounds were found to be non-toxic on tissues after their use since they did not inhibit the growth of micro-vessels in cultures treated with VEGF. Unlike the PI-88 compounds, PG500 series compounds showed better or at least comparable potent anti-tumor capacity (Dredge et al, 2010).

PG500 series compounds showed that their use could be extended to heparanase activity inhibition by remodeling the extra-cellular matrix, especially since they do not induce cytotoxicity in the models used for this study. In examining PG500 compounds’ applicability in clinical cancer settings, especially with regards to inhibiting metastasis and tumor growth, it was found that PG547, PG546, and PG545 reduced the development of tumors, as well as metastatic nodule counts. Compared to Tyrosine kinase inhibitors that accelerated metastasis in the mice models, PG500 series compounds proved they could be a new therapeutically in cancer treatment (Dredge et al, 2010).