Targeting ADAM17 Sheddase Activity in Cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• ADAM17 (a disintegrin and metalloprotease 17) is a sheddase enzyme.
• It releases ectodomains of membrane proteins, regulating growth factors, cytokines, and adhesion molecules.
• ADAM17 activity is implicated in physiological processes and pathological conditions like cancer progression.

Purpose of the Study:

• To review ADAM17 biology.
• To focus on its role in cancer development and progression.
• To explore the therapeutic potential of ADAM17 inhibitors in cancer treatment.

Main Methods:

• Review of recent literature on ADAM17 biology and inhibitors.
• Analysis of preclinical studies involving small molecule inhibitors, monoclonal antibodies, and gene silencing techniques.
• Evaluation of therapeutic strategies targeting ADAM17 in various cancer models.

Main Results:

• ADAM17 inhibitors demonstrated efficacy in preclinical studies.
• These inhibitors reduced cancer cell growth, invasiveness, and sensitized cells to other therapies.
• Specific approaches include small molecule inhibitors, monoclonal antibodies, and RNA interference.

Conclusions:

• ADAM17 inhibitors represent a promising therapeutic strategy for cancer.
• Repositioning ADAM17 inhibitors from anti-inflammatory to anti-cancer agents is suggested, particularly for EGFR ligand-dependent cancers.
• Future research should investigate short-term combination therapies involving ADAM17 inhibitors and conventional anti-cancer treatments.