Lung cancer has the highest cancer-related mortality rate worldwide, mainly because of late diagnosis and the emergence of treatment resistance as a result of tumor heterogeneity. Tumor cells within the same tumor respond differently to treatment. It is now known that this is partly driven by cancer stem cells that are under the control of NOTCH signaling, a pathway found overexpressed in many types of cancer and associated with worse outcomes. The hypothesis was that by blocking the NOTCH signaling pathway, the specific resistant tumor cell population could be targeted, and when combined with other therapies that target the bulk of the tumor (chemotherapy and/or radiotherapy), treatment outcome would improve. The findings indicate that NOTCH receptor blockade in cultured tumor cells, and in vivo in human tumors grown in mice, in combination with chemotherapy, radiation, or chemoradiation, delays growth of lung cancer and increases survival of mice. Similar results were obtained with a rare but aggressive model for brain cancer (glioblastoma multiforme). This means that combination treatments including Notch inhibition can benefit different types of cancer which have an active NOTCH signaling pathway.
|Award date||3 Jul 2018|
|Place of Publication||Maastricht|
|Publication status||Published - 2018|