The importance of being genotyped
Personalized medicine for small cell lung cancers
Small cell lung cancer is an aggressive type of cancer and can progress in very different, individual ways but so far no targeted therapy has been approved. By designing a mouse model mimicking a human disease phenotype, scientists discovered a promising combination therapy.
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Small cell lung cancer is an aggressive type of cancer with an extremely low survival rate, since many of the patients rapidly develop resistance against chemotherapy. However, standard therapy has hardly changed over the last 40 years. Furthermore, a detailed characterization of the course of therapy of single tumors can only be carried out insufficiently, even though the disease can progress in very different, individual ways. In close cooperation with the team of Trudy Oliver from Huntsman Cancer Institute in Utah, e:Med team leader Professor Martin Sos and Professor Roman Thomas (MILES and SMOOSE) now have discovered, that for patients with a particular genetic alteration a new and very promising combination therapy can be applied. Earlier studies have shown that among most patients the tumor suppressor genes RB1 and TP53 are non-functional. In addition, in some patients the oncogene MYC is to be found overactive, which is associated with a poor prognosis. Why these tumors are particularly aggressive is not yet clear. By means of a newly developed mouse model with this exact combination of mutations the scientists from Cologne were able to detect the molecular mechanisms of tumor differentiation and study new therapies. Within a very short time the mice develop lung tumors and show a specific expression pattern of characteristic neuroendocrine markers, which the scientists have also found in human samples. Murine metastases develop quickly, which is similar to the situations in humans. This mouse model is ideal for developing the best possible therapies and subsequently provides patients with individual treatment. Tests indicate that tumors show very good response to chemotherapy, but rapidly form treatment resistances. Additional MYC inhibition (by aurora kinase inhibitors) prevents relapse and allows chemotherapy to be effective. Precisely this specific therapy may be applied in future to treat small cell lung cancer patients with high MYC expression. The study shows the importance of investigating the background of diseases in order to establish personalized therapies.
Mollaoglu, G., Guthrie, M.R., Böhm, S., Brägelmann, J., Can, I., Ballieu, P.M., Marx, A., George, J., Heinen, C., Chalishazar, M.D., Cheng, H., Ireland, A.S., Denning, K.E., Mukhopadhyay, A., Vahrenkamp, J.M., Berrett, K.C., Mosbruger, T.L., Wang, J., Kohan, J.L., Salama, M.E., Witt, B.L., Peifer, M., Thomas, R.K., Gertz, J., Johnson, J.E., Gazdar, A.F., Wechsler-Reya, R.J., Sos, M.L., Oliver, T.G., 2017. MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition. Cancer Cell. dx.doi.org/10.1016/j.ccell.2016.12.005