Novelty:
Application of radioiodine therapy for the treatment of undifferentiated thyroid cancer and melanoma facilitated by induction of iodide-handling genes via dual suppression of PI3K/Akt and MAP kinase pathways
Value Proposition:
Thyroid cancer is typically treated by radioiodine therapy, which exploits the unique capability of thyroid cells to import and metabolize iodine. However, while differentiated thyroid cancers are usually curable, poorly differentiated or undifferentiated thyroid cancer (UTC) to date has very poor prognosis because of genetic alterations in the PI3K/Akt and MAP kinase pathways. Hence, this invention provides a means to dually suppress the PI3K/Akt and MAP kinase pathways, thereby synergistically inhibiting tumor growth as well as re-expressing iodide-handling genes in UTCs. In addition, similar effects were also observed in melanoma cells. Other advantages include:
• Simultaneous inhibition of the PI3K/Akt and MAP kinase pathways has synergistic anti-cancer effect
• Highly efficient cytotoxic effect versus cytostatic effect achieved by inhibition of individual pathways
• Several specific, potent and safe inhibitors are well-characterized and available
• Iodide-handling gene transfer allows radioiodine therapy of melanoma and possibly other extra-thyroidal cancers
Technical Details:
Johns Hopkins researchers have identified a novel strategy to block tumor growth and permit radioiodine therapy of UTC and human melanoma by the simultaneous suppression of the PI3K/Akt and MAP kinase pathways using specific inhibitors and siRNA molecules. PI3K/Akt and MAP kinase pathways are major regulators of cell proliferation; however, in cancer tissues they commonly harbor genetic mutations that result in cell cycle dysregulation and tumorigenesis. While inhibition of each pathway individually fails to show significant clinical responses, dual ablation by either the application of specific inhibitors or siRNA knockdown has a dramatic synergistic effect and results in arrest of tumor growth. Moreover, a stimulation of iodide-handling gene expression was observed in UTCs as well as melanoma cells, which thereupon became sensitive to radioiodine therapy. Taking into account the availability of well-studied and safe inhibitors, this presents a promising new approach to efficiently cure thyroid cancer and melanoma using the conventional radioactive iodine therapy.
Looking for Partners:
To develop and commercialize the technology as a synergistic and robust therapeutic of thyroid cancer and melanoma by conventional radioiodine therapy.
Stage of Development:
Pre-clinical
Data Availability:
Animal data
Publications/Associated Cases:
J Clin Endocrinol Metab. 2008 Aug;93(8):3106-16.
