Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 29 1 2026 01 01 A Review of Exhaled Volatile Organic Compounds as Emerging Diagnostic Tools for Gastrointestinal Malignancies 35 43 10.34172/aim.34980 EN Amirreza Ghafourian https://orcid.org/0009-0007-7584-4952 Masoomeh Hamdi https://orcid.org/0009-0003-8954-5452 Maryam Rayatpisheh Ramin Shakeri Naser Ahmadbeigi Shokoofeh Borzabadi Abolghasem Jouyban Reza Ghanbari https://orcid.org/0000-0003-3876-7584 REVIEW 10.34172/aim.34980 2025 08 19 2025 11 19 Gastrointestinal cancers encompass a range of malignancies, including esophageal, gastric, esophagogastric, hepatocellular, pancreatic, and intestinal cancers. Considering the prevalence of these cancers, alongside their fatal nature, and the nonspecific symptoms that often arise in the advanced stages, developing a non-invasive screening/diagnostic method capable of detecting cancer early is in high demand. Exhaled breath serves as an accessible source of biomarkers, including volatile organic compounds (VOCs), a promising type of diagnostic marker. This method requires a sample as small as five breaths. Exhaled breath analysis is conducted using different mass spectrometry methods coupled with nano sensors or neural networks. Furthermore, innovative devices like electronic noses have also shown great promise in diagnosing different types of cancers. These biomarkers show potential in reliably differentiating between healthy individuals and cancer patients. Additionally, these compounds can be utilized for cancer staging and monitoring treatment response. However, certain fallbacks persist in differentiating malignant from pre-malignant conditions. Despite the promise of this diagnostic approach, certain limitations, such as variations in VOC profiles across different populations, lack of standardized collection protocols, and absence of established universal reference standards, underscore the need for proper standardization and large-scale, multi-center validation studies.