EXT-HOSSAM HAICK · Developing and studying artificial olfactory systems based on nanocomposite materials for detecting cancer via breath samples

Final Activity Report Summary - EXT-HOSSAM HAICK (Developing and Studying Artificial Olfactory Systems Based on Nanocomposite Materials for Detecting Cancer via Breath Samples)

Lung Cancer (LC) is the most lethal cancer, accounting for 28% of cancer deaths globally. Detecting LC in its early stages can be expected to increase the 5-year-survival rate by 3-4 times. Unfortunately, LC diagnostic tests currently available are not suited for widespread screening as they are not efficient in terms of time and costs and are unpleasant for the patient, and not free of complications. In the course of the FP6' Marie Curie Excellent Grant, we have developed a highly-sensitive and fast-response sensors array based on metallic nanoparticles, carbon nanotubes and silicon nanowires. Using this technology we have shown, both in laboratory and clinical tracks, an excellent ability to distinguish the breath of lung cancer patients from that of healthy individuals in the presence of confounding factors. Furthermore, we have compared the volatile biomarkers in lung cancer patients to breast cancer, colon cancer, and prostate cancer patients, and to healthy controls. The results showed that the presence of another cancer did not mask the lung cancer breath volatile biomarkers. In addition to the above-mentioned achievements, we have tested the sensitivity of the device to some important non-cancer related volatile biomarkers in the breath, using breath samples from a heterogeneous group of healthy controls, composed of various distinct subgroups. Towards this end, breath samples of healthy subjects were diagnosed by an array of the developed sensors in conjugation with pattern recognition methods and correlated with pertinent confounding factors. The results revealed that our set of sensors was not influenced by the different confounding factors of the tested subjects: gender, age, smoking, family cancer history, drug treatment, pollutant exposure, food additive, or place of birth. The analysis showed no relation of the food and beverage consumed to the pattern data received, and, also, no influence of the time lag between the sampling and both the last meal and the last coffee. In a proof-of-concept study towards the end of the grant period, we have shown, using the technology developed in the current project that healthy, cancer and dysplasia (i.e., the earliest form of pre-cancerous lesion recognisable in a biopsy) states can satisfactorily distinguished from each other through exhaled breath. Additionally, volatile biomarkers emitted from in-vitro small cell LC (SCLC), non-small cell LC (NSCLC) and controls can be distinguished by the developed technology. Significantly, the volatile biomarkers emitted NSCLC cell lines that exhibit EGFR mutation (mut) which can be distinguished from NSCLC cell lines that are EGFR wild type (wt). The implication of this finding is the ability of the developed technology to assist in easy, inexpensive and early detection of the LC group that can benefit from oral targeted therapy (e.g. EGFR tyrosin kinase inhibitors). In contrast to the "aggressive" conventional chemotherapy, oral targeted therapy is free of serious side effects. The developed technology in the current FP6 EXT project would be suitable for use outside of specialist settings and would significantly reduce costs in health budgets. In addition, it could be used for immediate diagnosis of fresh LC tissues in operating rooms, where a dichotomic diagnosis is crucial to guide surgeons. The easy-to-use (no medical specialists required) technology detects lung cancer based on a change in the blood chemistry and/or metabolic activity (which is reflected in the chemical composition of the exhaled breath and cell/tissue headspace) rather than by tumour imaging, thus permitting earliest cancer detection i.e. before a tumour of detectable size has formed. The effectiveness of the developed EXCT technology in detecting LC volatile biomarkers specifically and selectively will provide a launch pad for identifying other types of cancer from simple analysis of clinical samples, including breast, colon, and prostate cancers.

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