TARGETS

The identification and the understanding of disease driver genes, such as KRAS in oncogenesis, is the cornerstone of targeted therapies, particularly gene therapy. Antapodia Nanotherapeutics pioneered the identification of a series of "Master Invadopodial Regulators (MIRs)" that drive the biogenesis and the functions of invadopodia in invasive cancer cells; importantly, they are exclusively or predominantly expressed in cancer cells but not in normal cells, making them ideal and safe therapeutic targets (Table 1). Targeting MIRs provides a unique opportunity to selectively block invadopodia formation and inhibit cancer aggressiveness and metastasis.

Table 1. Antapodia's Targets

Molecular target 

Localization

Function

Molecular signaling

Expression in

Target diseases

MIR-1

Submembranous region in invadopodia

Invadopodial biogenesis/Wnt activation

Wnt/planar cell polarity

Invasive cancer cells (exclusively)

PDAC, GAC, PC, HCC, TNBC

MIR-2

Invadopodial surface

Promotes invadopodial functions

PKC/small GTPase/EMT

Invasive cancer cells (predominantly)

PDAC, GAC, PC, TNBC

 

PDAC: pancreatic ductal adenocarcinoma; GAC: gastric adenocarcinoma; PC: peritoneal carcinomatosis; HCC: hepatocellular carcinoma; TNBC: triple-negative breast cancer.

MIR-1

MIR-1 is specifically localized to the submembranous region of nascent invadopodia on invasive cancer cells across different types of human cancers. Molecular studies reveal that MIR-1 promotes the assembly of a developmentally conserved planar cell polarity protein complex to promote the initiation of invadopodia (Figure 1). Another molecular function of MIR-1 the regulation of canonical Wnt signaling in cancer cells. Accordingly, the genetic knockdown of MIR-1 can simultaneously block the invadopodial formation in invasive cancer cells and the growth of cancer cells, thereby inhibiting the growth and the invasiveness of the primary tumor as well as the development of distant metastasis.

MIR-2

MIR-2 is a transmembrane receptor that is predominantly localized to the invadopodial surface of invasive cancer cells. Upon ligand ligation, MIR-2 activates multiple downstream pathways, including protein-kinase C, small GTPases, and epithelial-mesenchymal transition (EMT) pathways, to promote the invadopodial functions and cell invasiveness. Similar to the effect of MIR-1 knockdown, knockdown of MIR-2 blocks the formation of invadopodia in invasive cancer cells, thereby inhibiting cancer invasiveness and metastasis.                                                                                                                                                                                                                                                                                       

Figure 1. Schematic depicting the localization and the molecular functions of Antapodia’s targets

Figure 1. Antapodia Nanotherapeutics’s proprietary invadopodia targets MIR-1 and MIR-2.
Copyright © Antapodia Nanotherapeutics, Inc. All Rights Reserved

Search