Distinct Capabilities in NAD Metabolism Mediate Resistance to NAMPT Inhibition in Glioblastoma
Richard Perryman, TszWing Chau , John De-Felice, Kevin O’Neill and Nelofer Syed.
Patients with glioblastoma have very few treatment options; even with best treatment, including surgery, radiotherapy and chemotherapy, overall survival time is poor. Cancer cells need very high levels of energy to maintain their rapid growth, and a key component of this is a chemical called NAD. We can block the production of NAD in cancer cells by using inhibitors of specific substances in cells, limiting the growth of the tumour. This study highlights how cancer cells might exhibit resistance to inhibitors of NAD production, and how we can select a subset of patients that are uniquely responsive to these types of inhibitors. Furthermore, this study demonstrates that these inhibitors improve the effectiveness of the type of chemotherapy most often used to treat patients with aggressive brain tumours, called temozolomide. Patients may therefore benefit from the use of inhibitors of NAD production in combination with temozolomide.