DOI: 10.1101/492306Dec 10, 2018Paper

A Priori Activation of Apoptosis Pathways of Tumor (AAAPT) Technology: Sensitization of Tumor Cells Using Targeted and Cleavable Apoptosis Initiators in Gastric Cancer.

BioRxiv : the Preprint Server for Biology
Raghu S Pandurangi

Abstract

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. The principle route of desensitization includes activation of survival pathways (e.g. NF-kB, PARP) and downregulation of cell death pathways (e.g. CD95, ASK1). As a result, it requires high dose of therapy to induce cell death which, in turn damages normal cells through the collateral effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing low-responsive and resistant tumor cells. Here we report a novel tumor sensitizer derived from the natural Vitamin E analogue (AMP-001). The drug design is based on a novel “A priori activation of apoptosis pathways of tumor technology (AAAPT) which is designed to activate cell death pathways and inhibit survival pathways simultaneously. It involves an inbuilt targeting vector which targets tumor specific Cathepsin B, overexpressed by many cancers including gastric cancer. Our results indicate that AMP-001 sensitizes gastric cancer cells which resulted in expanding the therapeutic index of fron...Continue Reading

Related Concepts

Allergens
Malignant Neoplasms
Cell Death
Down-Regulation
Doxorubicin
Genetic Vectors
Malignant Neoplasm of Stomach
Neoplasms
NF-kappa B
Apoptosis

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