Our focus on making blood-brain barrier penetrant compounds offers a distinct advantage for possible treatments for brain cancers and peripheral tumours capable of metastasizing to the brain. In addition, mechanisms selected for modulation may be relevant to peripheral cancers and are being progressed for non-CNS related tumours.

Glioblastoma multiforme (GBM) is the most malignant type of astrocytoma (grade 4). Although GBM is the most common form CNS tumour, it represents a rare disease. Maximal surgical resection in combination with chemo- and radiotherapy is the current 'standard-of-care' for GBM. Since median 2-year survival rate is poor there is a clear need for effective therapies for both newly diagnosed and recurrent tumours. The difficulty in identifying efficacious treatments lies in the fact that the tumours are very heterogeneous and highly invasive. Classical cell systems often used for drug screening often do not show the characteristics observed in clinical samples.

Siena Biotech uses proprietary GBM cell lines and employs assay systems, both in vitro and in vivo, that more closely mimic aspects of the complexity of glioblastoma multiforme.

Oncogenesis occurs through the acquisition and selection of multiple somatic mutations-each contributing to the growth, survival and spread of cancer. Key attributes of the malignant phenotype, such as unchecked proliferation and cell survival, can be driven by very specific aberrations ( e.g. β-catenin in colorectal carcinomas; bcr-abl in chronic myelogenous leukemias (CMLs)). To extend the value and applicability of compounds discovered in our neuro oncology portfolio projects, a selection of in vitro and in vivo peripheral tumour models (such as colon, breast, pancreas, prostate, lung etc.) are used for drug efficacy assessment.

Siena Biotech's strategy is to:

-	Prioritize the use of orthotopic tumour models for compound testing, detectable by MRI.
-	Generate where possible luciferase labeled tumor cell systems to facilitate sensitive compounds' efficacy detection of tumour growth, invasion and metastasis using bioluminiscence imaging (in vitro and in vivo).