Magnesium and tumors: ally or foe?
Magnesium plays a crucial role in many cell functions such as energy metabolism, protein and DNA syntheses, and cytoskeleton activation. Proliferating cells have long been known to contain more magnesium than quiescent cells, and experimental conditions that decreased magnesium availability affected cell proliferation rate. There is little information about how tumor growth influenced systemic availability of magnesium in a patient, nor is it clear whether treatment-associated changes of magnesaemia influenced tumor growth and dissemination. Hypomagnesaemia is observed during multi-agent therapies with cisplatin or the anti-EGFR antibody, cetuximab. The latter was shown to cause hypomagnesaemia by impeding EGF-dependent activation of TRPM6, the main cation channel responsible for Mg transcellular absorption in the intestine and kidney. Limited observations also suggest that hypomagnesaemia could favorably influence tumor response to cetuximab. All such findings brought magnesium into the arena of clinical oncology, but potential caveats should be kept in mind before considering practical implications. We briefly review that magnesium causes pleiotropic, often diverging effects on tumor growth, vascularization, and metastatization, such that both favorable and unfavorable effects can be identified. Inflammatory responses to hypomagnesaemia should also be considered. Translating biology into clinical facts will therefore require a deeper understanding of such a complexity.
Wolf
Federica I
FI
Università Cattolica del Sacro Cuore, Istituto di Patologia generale e Centro di Ricerche Oncologiche Giovanni XXIII, Facoltà di Medicina A. Gemelli, Roma, Italy. fwolf@rm.unicatt.it
Cittadini
Achille R M
AR
Maier
Jeanette A M
JA
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008274:Magnesium / Q000097:blood / Q000378:metabolism*; D008297:Male; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008274:Magnesium; D000068818:Cetuximab; D002945:Cisplatin