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 Biotherapeutics 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 Biotherapeutics's Targets

Molecular target 

Localization

Function

Molecular signaling

Specific expression in/on

MIR-01

Submembranous region in invadopodia

Invadopodial biogenesis/Wnt pathway activation

Planar cell polarity/Wnt signaling

Invasive cancer cells

MIR-02

Invadopodial surface

Promotes invadopodial signaling & functions

Various kinase and small GTPases

Invasive cancer cells

MIR-03 Invadopodial surface Promotes peri-invadopodial proteolysis MMP activation Invasive cancer cells

 

MIR-01

MIR-01 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-01 promotes the assembly of a developmentally conserved planar cell polarity protein complex to promote the initiation of invadopodia (Figure 1). MIR-01 also regulates canonical Wnt signaling in cancer cells. The genetic knockdown of MIR-01 simultaneously blocks the invadopodial formation of invasive cancer cells and the growth of cancer cells, thereby inhibiting the invasive growth of primary tumors as well as the development of distant metastasis.

MIR-02

MIR-02 is a transmembrane receptor that is predominantly localized to the invadopodial surface of invasive cancer cells. Upon ligand ligation, MIR-2 activates various downstream pathways, including protein-kinase C, small GTPases, and epithelial-mesenchymal transition (EMT) pathways, to promote the invadopodial functions and cell invasiveness (Figure 1). Similar to the effect of MIR-01 knockdown, knockdown of MIR-02 blocks the formation of invadopodia in invasive cancer cells, thereby inhibiting cancer invasiveness and metastasis.                                                                                                                                                                                                                                                                                       

MIR-03

MIR-03 is a secreted protein that is specifically attached to the invadopodial surface of invasive cancer cells. MIR-03 promotes the peri-invadopodial proteolysis by activating various matrix metalloproteases (MMPs), thereby facilitating the invasive behavior of cancer cells (Figure 1).   

 

 

 

 

 

 

 

 

 

                                                                                                 

Figure 1. The localization and molecular functions of Antapodia Biotherapeutics’s MIR targets

Figure 1. Antapodia Nanotherapeutics’s proprietary invadopodia targets MIR-1 and MIR-2.
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