On the subventricular zone origin of human glioblastoma

The cancer stem cell theory posits that a small subset of cancer cells with self-renewing capacity, popularly known as cancer stem cells and experimentally defined as tumor-initiating cells, maintains the tumor with its heterogeneous lineages of cancer cells (1,2). Identification of these cells is critical for effective cancer therapy, because often after conventional radiation and chemotherapies, which predominantly eradicate proliferative tumor cells, the therapy-resistant cancer stem cells reconstitute the tumor, heralding clinical relapse and therapy failure (2,3). Since the discovery of therapy-resistant glioblastoma stem cells that can initiate tumors (4) and cause post-therapy tumor recurrence (5), the glioblastoma cell of origin, which holds the key to improving the meager arsenal of effective glioblastoma therapies and the median 16-month patient survival (6,7), has remained elusive. The recent work by Lee and colleagues (8) provides a direct evidence supporting the long-standing hypothesis that cells resident in the subventricular zone (SVZ), a neural stem cell niche which lies in the lateral walls of the lateral ventricles in the brain, are the cells of origin for glioblastoma in humans (9). Their work supports that the cancer stem cell model holds true in the case of glioblastoma and has important implications for exploring novel therapeutic approaches in its treatment