Shiga Toxins as Antitumor Tools

Area of Science:

• Microbiology
• Toxicology
• Biomedical Engineering

Background:

• Shiga toxins (Stxs), also known as Shiga-like toxins (SLT) or verotoxins (VT), are cytotoxic proteins from *Shigella dysenteriae* and Shiga toxin-producing *Escherichia coli* (STEC).
• Stx infections lead to bloody diarrhea and hemolytic uremic syndrome (HUS).
• At the cellular level, Stxs inhibit protein synthesis after binding to the Gb3 receptor, triggering stress responses like RSR, UPR, autophagy, and apoptosis.

Purpose of the Study:

• To review the potential of Shiga toxins (Stxs) for biomedical applications, particularly in cancer therapy and imaging.
• To explore the exploitation of Stxs' host cell targeting and cytosolic delivery mechanisms for therapeutic purposes.
• To summarize current research and development of engineered Stxs for medical use.

Main Methods:

• Literature review of studies on Shiga toxins (Stxs) and their biomedical applications.
• Analysis of Stxs' mechanism of action, including Gb3 receptor binding and protein synthesis inhibition.
• Examination of Stxs receptor (Gb3/CD77) expression in various cancers, including Burkitt's lymphoma and solid tumors.

Main Results:

• Shiga toxins (Stxs) possess unique cellular targeting and cytosolic delivery capabilities.
• The Stxs receptor, Gb3/CD77, is highly expressed on Burkitt's lymphoma cells and other solid tumors.
• Engineered Stxs are under investigation for cancer treatment and imaging applications.

Conclusions:

• The specific targeting and delivery mechanisms of Shiga toxins (Stxs) offer promising avenues for developing novel cancer therapies.
• Exploiting the Gb3 receptor's overexpression in certain cancers could enable targeted drug delivery.
• Ongoing research into engineered Stxs holds potential for advancing cancer treatment and diagnostics.