Radiotherapy-induced gut toxicity: Involvement of matrix metalloproteinases and the intestinal microvasculature

Area of Science:

• Gastroenterology
• Oncology
• Radiology

Background:

• Radiotherapy-induced gut toxicity (RIGT) causes gastrointestinal mucosal damage, leading to symptoms like diarrhea, pain, and rectal bleeding.
• The precise mechanisms underlying RIGT remain complex and not fully elucidated.
• The microvasculature's role in chemotherapy-induced gut toxicity (CIGT) and RIGT is recognized but mechanistically underexplored.

Purpose of the Study:

• To review existing literature on the endothelium and matrix metalloproteinases (MMPs) in RIGT.
• To further elucidate the complex pathobiology of radiotherapy-induced gastrointestinal damage.
• To explore the potential role of MMPs in the microvascular mechanisms of RIGT.

Main Methods:

• Literature review of studies investigating RIGT.
• Analysis of research on matrix metalloproteinases (MMPs) in gastrointestinal toxicity.
• Examination of studies implicating the microvasculature in radiotherapy side effects.

Main Results:

• Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are identified as key markers in both RIGT and CIGT.
• The endothelium is consistently implicated in the development of toxicities following both chemotherapy and radiotherapy.
• RIGT involves damage to the gastrointestinal mucosa, with symptoms varying by exposure area.

Conclusions:

• Matrix metalloproteinases (MMPs) are proposed as key regulators of endothelial mediators.
• MMPs may play a significant role in damaging the intestinal microvasculature after radiotherapy.
• Further research is needed to fully understand the endothelial and MMP pathways in RIGT.