Abstract

Abstract Lung cancer remains a leading cause of cancer-related mortality globally, necessitating innovative approaches for early detection and improved understanding of its metabolic landscape and consequences. Secondary Electrospray Ionization Mass Spectrometry (SESI-MS), an innovative analytical technique, has emerged as a powerful tool for the analysis of volatile organic compounds (VOCs) associated with various diseases, from metabolic disorders to bacterial infections. In this proof-of-concept study, we first utilized SESI-MS analyses of four representative lung cancer cells of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) to demonstrate its capability to profile VOCs released by lung cancer cells. The technique allows for real-time, non-invasive analysis of the headspace above cultured cells, enabling the detection of unique VOC signatures associated with different lung cancer subtypes. Meanwhile, SESI-MS also facilitated the discrimination specific cells based on distinct VOC patterns. Furthermore, we also performed cisplatin treatment experiments and observed the metabolic signature shift post drug treatment. These results collectively offered potential applications in early diagnosis and personalized treatment strategies. Next, we continued with in vivo investigations to further extend the utility of SESI-MS in lung cancer research. Animal models, mimicking human lung cancer pathophysiology, have been subjected to SESI-MS analysis to identify volatile biomarkers indicative of tumor development and progression. Several representative cancer drug treatments were performed to the lung cancer mice model, and the drug-induced responses were also monitored via SESI-MS breath analyses. The in vivo SESI-MS approach detected many interesting breath VOC features that could provide valuable insights into the dynamic changes in VOC profiles during various stages of lung cancer, and therefore has the potential to offer a deeper understanding of the disease's metabolic alterations and potential avenues for targeted therapeutic interventions. In conclusion, SESI-MS-based volatile analysis presents a robust and versatile approach for investigating lung cancer, and our ongoing work has the potential to bridge the gap between in vitro and in vivo models for better translational research outcomes. The detection of unique VOC signatures associated with lung cancer cells and tumors holds significant promise for early detection, subtype classification, and monitoring of treatment responses. As technology continues to advance, SESI-MS stands poised to play a pivotal role in transforming the landscape of lung cancer diagnostics and research. Citation Format: Jiangjiang (Chris) Zhu, Fouad Choueiry. Secondary electrospray ionization mass spectrometry for volatile analysis of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4433.

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