This summer, Vitali et al. published an article in the Open Access Journal Cancers in which they assessed anticancer combination to treat neuroendocrine tumors (NETs) using in vitro models (2D + 3D cultures in BIOMIMESYS hydroscaffolds).
A NET arises in the specialized cells of the neuroendocrine system, which have traits of both hormone-producing endocrine cells and nerve cells. These NETs can begin in any part of the body, including the lung (called pulmonary neuroendocrine tumors, or PNTs), the gastrointestinal tract and the pancreas (called pancreatic NET, or PAN-NET). In their article, the authors focused on PNTs and PAN-NETs.
NETs often show resistance to treatments. Everolimus is an inhibitor of m-TOR (mechanistic Target Of Rapamycin, a serine/threonine-protein kinase) that is used against NETs, but some patients develop resistance. The mechanism leading to this resistance is thought to be a negative feedback loop leading to the activation of Akt signalling. For this reason, the authors tested Metformin – since it is able to inhibit mTOR pathway – as an additional medicine to everolimus. In their study, metformin and everolimus were tested in combination.
The results showed that this combination everolimuns + metformin was more effective than monotherapy to conteract NET development in vitro, as shown by a reduced NET spheroid growth in BIOMIMESYS and mTOR phosphorylation in different NET cell lines.
Even if the mechanism was found different (Akt-dependent or independent) depending on the cell type, mTOR suppression was successful. For this reason, the authors propose the combination everolimuns + metformin to be tested in patients suffering from NETs.