AVJ16 inhibits lung carcinoma by targeting IGF2BP1

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Insulin-like Growth Factor 2 Binding Protein 1 (IGF2BP1) is an oncofoetal RNA binding protein (RBP) implicated in various cancers.
• The precise mechanisms of RBPs in cancer progression are not fully elucidated.
• Targeting specific RBPs offers a potential strategy for novel cancer therapies.

Purpose of the Study:

• To investigate the effects of a novel small molecule inhibitor, AVJ16, on IGF2BP1 activity and its downstream consequences in cancer cells.
• To evaluate the therapeutic potential of AVJ16 in preclinical cancer models.

Main Methods:

• Treatment of cancer cells and xenografts with AVJ16.
• Analysis of RNA binding, RNA expression, and protein expression.
• Assessment of cellular phenotypes including colony formation, invasion, spheroid growth, apoptosis, and cell death.
• Evaluation in syngeneic LUAD xenografts and human organoid models.

Main Results:

• AVJ16 treatment significantly downregulates pro-oncogenic signaling pathways (Hedgehog, Wnt, PI3K-Akt) by affecting IGF2BP1 RNA binding, RNA, and protein expression.
• AVJ16 inhibits colony formation, invasion, and spheroid growth while enhancing apoptosis and cell death in IGF2BP1-expressing cells.
• AVJ16 prevents tumor growth in LUAD xenografts and induces cell death in IGF2BP1-positive LUAD organoids.

Conclusions:

• AVJ16 effectively inhibits IGF2BP1 function, leading to reduced tumor growth and increased cancer cell death.
• AVJ16 demonstrates significant potential as a targeted therapeutic agent for tumors expressing IGF2BP1.
• This study highlights the therapeutic value of targeting IGF2BP1 in cancer treatment.