The metallome of lung cancer and its potential use as biomarker

Carcinogenesis is a very complex process in which metals have been found to be critically involved. In this sense, a disturbed redox status and metal dyshomeostasis take place during the onset and progression of cancer, and it is well-known that trace elements participate in the activation or inhibition of enzymatic reactions and metalloproteins, in which they usually participate as cofactors. Until now, the role of metals in cancer have been studied as an effect, establishing that cancer onset and progression affects the disturbance of the natural chemical form of the essential elements in the metabolism. However, it has also been studied as a cause, giving insights related to the high exposure of metals giving a place to the carcinogenic process. On the other hand, the chemical species of the metal or metallobiomolecule is very important, since it finally affects the biological activity or the toxicological potential of the element and their mobility across different biological compartments. Moreover, the importance of metal homeostasis and metals interactions in biology has also been demonstrated, and the ratios between some elements were found to be different in cancer patients; however, the interplay of elements is rarely reported. This review focuses on the critical role of metals in lung cancer, which is one of the most insidious forms of cancer, with special attention to the analytical approaches and pitfalls to extract metals and their species from tissues and biofluids, determining the ratios of metals, obtaining classification profiles, and finally defining the metallome of lung cancer.This research was funded by the projects CTM2015-67902-C-1-P from the Spanish Ministry of Economy and Competitiveness, and P12-FQM-0442 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government, Spain). Projects Neumosur (8/2012 and 9/2015) and SEPAR (124/2012 and 091/2016). Belén Callejón Leblic thanks the Ministry of Education, Culture and Sport for a predoctoral scholarship. Finally, authors are grateful to FEDER (European Community) for financial support, grants number UNHU13-1E-1611 and UNHU15-CE-3140