Investigating molecular mechanisms driving differentiation in ALK-positive neuroblastoma

There is an urgent need to identify novel therapies for high-risk neuroblastoma (NB), a childhood cancer. Survival rates for high-risk (HR) NB are disappointingly low. In addition, cytotoxic standard therapies cause serious lifelong side effects and increased risk for secondary tumors.

To improve patient outcome, we need to understand the initiation and progression of Anaplastic Lymphoma Kinase (ALK) driven NB. Moreover, we need to understand this in relation to the differentiation process.

To address the underlying cellular and molecular mechanisms, we are focusing on  understand how perturbation of normal differentiation programs in the neural crest leads to the development and persistence of NB despite current aggressive treatment regimes.

Our aims are: (i) comprehensive efforts to decode key molecular events underlying the differentiation process. (ii) Use our findings to tailor optimized therapeutic treatment options for NB patients, with initial focus on ALK-driven neuroblastoma.

Are goal is to generate preclinical proof-of-principle results that can be translated in to the clinic.The time-frame for this application is 4-years.

We will employ genetic engineering tools (cell cultures and GEMMs) together with PXDs, molecular and biochemical tools and assays.Project leader: Bengt Hallberg, Prof. and PI. Laboratory manager: Dan Lind BSc. Researcher: Jikui Guan. Ph.D students: Edit Zentenius, MD., Wasi Alam, BSc. Post-docorals; Tzu-Po Chuang, Ph.D, Wei-Yun Lai, Ph.D