| |
| |
| |
| |
Publications |
| |
Inhibiting Protein Translation
The innovative foundation of Egenix’s cancer program is based on development small molecule drugs that block the ability of specific RNAs (the RNA is not “translated”) to produce specific proteins which are critical for cancer growth and survival. The drugs mediate this activity through inhibition of “translation initiation factors”. The translation initiation factors are essential elements for synthesis of multiple cancer promoting proteins including those that stimulate cancer growth, metastasis, angiogenesis (tumor blood vessel growth), and suppression of apoptosis (programmed cell death).
Cancer growth and metastasis requires an interplay of numerous and diverse gene products (proteins) including oncoproteins (c-myc, cyclin D1), angiogenesis factors (VEGF), and apoptosis suppressors. The translation initiation factors eIF4E and eIF2α selectively promote the synthesis of these proteins and drive malignant growth and metastatic progression. eIF4E and eIF2α represent critical convergence points for regulation of key growth and metastasis genes. Blocking the activity of eIF4E and/or eIF2α dramatically suppresses malignant transformation, tumor growth, and metastasis. eIF4E and eIF2α are compelling cancer therapeutic targets because multiple processes required for cancer growth and metastasis are mediated by proteins that are regulated by these translation initiation factors.
“Proof of principle” in vitro and in animal models has been established. Our lead compounds, which block the activity of of eIF4E or eIF2α, have demonstrated potent activity against multiple cancer cell lines, anti-tumor activity in animal models, downregulation of oncogenes including cyclin D1, VEGF, and c-myc, and upregulation of apoptotic and tumor suppressor proteins. Importantly, there has been little effect of these compounds on synthesis of proteins essential for basic cell functions.
Egenix’s cancer therapeutics are expected to increase cancer cure rates or transform a fatal disease to a chronic illness with an improved quality of life. The drugs can also be used as preventive agents to decrease risk of cancer recurrence after surgery or to decrease the risk of cancer development in high risk patients.