Singapore, 13 October, 2008 - A new study led by the National Neuroscience Institute (NNI) and Singapore Institute for Clinical Sciences (SICS), A*STAR shows for the first time that primary brain tumors are caused by a minority group of cells that display a genetic profile distinct from that of the tumor bulk. This minority group of cells has reliably established a method of cryopreservation for these tumor-initiating cells (frequently termed "cancer stem cells"), thus facilitating the development of a brain tumor stem cell repository for future research and drug screening efforts. The findings have been accepted for publication in the esteemed journal Stem Cells.

Although malignant tumours are known to be made up of a variety of different cell types, this concept of cellular heterogeneity in the study and design of anti-cancer therapeutics has largely been ignored. Emerging evidence in recent years has established key culprit cells within the tumor mass - the "cancer stem cells", which are responsible for initiation and propagation of tumour growth. These cancer stem cells are notoriously resistant to radiation and chemotherapy. The latter adjuvant therapies, which preferentially target rapidly dividing cells thus end up eliminating the bulk of tumour cells but spare these stem cells which divide at a much slower rate.

Primary malignant brain tumors are devastating cancers with poor survival rates despite major advances in surgical technology and adjuvant therapies. The results of this study demonstrate the isolation of brain tumor stem cells from patient tumour samples, which are capable of re-creating tumour masses in mice. These implanted cells in the mouse brain eventually form tumours with morphology identical to that seen on the pathological analysis of patient specimens. These tumor cells-of-origin display genetic profiles completely distinct from the tumor bulk. Importantly, the researchers have found that different patients with similar tumor tissue pathology on microscopic examination display different genetic profiles in their cells-of-origin, the cancer stem cells. This has major implications as current treatment strategies are largely decided based upon classification systems tailored according to morphological characteristics of the tumour. The different genetic profiles of such tumor stem cells might explain variability of treatment response and points to the existence of different genetic brain tumor subtypes which one is unable to discern based on current classification systems.

As brain tumor stem cells constitute the minority of the tumor mass, a key challenge has been to create a stable collection of such cells to enable investigative efforts in drug screening. The researchers have established a method of cryopreservation that facilitates the establishment of a brain tumor stem cell repository.

The study is led by senior co-investigators – Dr. Carol Tang, a NNI research scientist and Dr. Christopher Ang Beng Ti, a neurosurgeon at NNI and clinical investigator with SICS, with collaborative efforts from the National University of Singapore, National Cancer Centre, Duke-NUS Graduate Medical School and Genome Institute of Singapore.

Both lead investigators are encouraged by the implications of their findings. On the uniqueness of the study, both investigators commented, "While most cancer stem cell studies in Singapore utilize genetically engineered mouse models, we have the advantage of starting from clinical specimens, and then finding that the cells reflect individual patient variability which cannot be captured in a single mouse model. This forces a re-evaluation of how drugs should be designed to deal with the different brain tumor subtypes. Without the cells, there is no science, so we now look forward to exciting days ahead". The brain tumor stem cell repository is now currently the subject of a drug screening effort with a major pharmaceutical company.