Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Cell surface proteases (ectoproteases) are enzymes crucial in physiological and pathological processes.
• Key ectoproteases like DPP4, FAP, APN, ADAM17, MMP2, and MMP9 are frequently overexpressed in cancers, contributing to tumor progression.
• These enzymes have been validated as significant therapeutic targets in oncology.

Purpose of the Study:

• To review current knowledge on ectoprotease inhibitors for cancer therapy.
• To highlight recent developments in novel and selective drugs targeting cancer-associated ectoproteases.

Main Methods:

• Literature review of ectoprotease inhibitors.
• Summary of small molecular weight inhibitors, peptide conjugates, prodrugs, and monoclonal antibodies.
• Analysis of clinical trial outcomes and emerging therapeutic strategies.

Main Results:

• Despite challenges in early clinical trials, the field of ectoprotease inhibitors is rapidly advancing.
• Development of more effective and selective inhibitors, including small molecules and biologics, is ongoing.
• Promising new therapeutic strategies targeting ectoproteases are emerging.

Conclusions:

• Ectoproteases represent a promising class of therapeutic targets for cancer treatment.
• Novel inhibitor strategies, including small molecules and antibody-based therapies, show potential for improved efficacy and selectivity.
• Continued research in ectoprotease inhibition may lead to significant advancements in cancer therapy.