She has directed many innovative studies in new therapies for neuroblastoma through the Children’s Oncology Group (COG) and the New Approaches to Neuroblastoma Therapy (NANT). Neuroblastoma is a cancer that often originates in the adrenal gland in the abdomen, but also may begin in nerve tissue in the neck, chest or pelvis. She and her colleagues in the COG have shown that the metastatic form of the disease can be best treated with intensive chemotherapy, bone marrow or stem cell transplantation, and then therapy to eliminate microscopic disease with the vitamin A derivative, 13-cis-retinoic acid along with immunotherapy with anti-GD2 antibody and cytokines.
The activities of the Paediatric Oncology Research lab focus on the biology and genetics of neuroectoderm-derived tumors such as neuroblastoma. Neuroblastoma is a typically paediatric and extremely heterogeneous tumour known to result from abnormal development of neural crest-derived sympathetic cells. Whereas low stage and infant tumours frequently undergo spontaneous remission or maturation, high stage tumors are metastatic, rapidly progress, and generally present a multi-drug and apoptosis-resistant phenotype associated to several genomic alterations. Using biochemical or global genomic approaches, we are interested to identify genetic alterations and deregulations in the apoptotic signalling pathways involved in the particular aggressive behaviour of advanced stage tumors, namely responsible for their proliferative (angiogenesis-related), apoptosis-resistant, and metastatic behaviour. In parallel, our objectives include the identification and characterisation of a drug-resistant, putative cancer progenitor neuroblastoma cell.
Since many years, her research activities are focused on the role of the tumor suppressor gene ATM (Ataxia Telangiectasia Mutated) in pediatric cancers. More recently, she and her colleagues of the Pediatric Oncology Lab, investiguate the role of ATM and its pathway in neuroblastoma.
Surgery remains an important step of the therapeutical strategy in paediatric oncology. I am involved since 15 years in this area and particularly interested in neuroblastoma and germ cell tumors. We have developed original surgical approach for cervicothoracic neuroblastoma and dumbbell neuroblastoma in close collaboration with neurosurgeons, orthopaedists and otolaryngologist. As a paediatric surgeon naturally involved in the treatment of congenital malformations, we are particularly interested in patients presenting tumour with a syndromic context or with a genetic predisposition to cancer (NEM, Wiedemann-Becwith, Denys-Drash…).
Prof. Frank Speleman has a longstanding experience in molecular genetics oriented research and increasingly applied high throughput genetic screening methods in the quest for new genetic defects in cancer and perturbed genetic networks as anchor points for novel therapies. He contributed to one of the major breakthroughs in both neuroblastoma (discovery of drugable ALK activating mutations) and T-cell acute lymphoblastic leukemia (PHF6 as a major tumor suppressor gene). Together with Jo Vandesompele, they are the inspirators of an intensive research program on noncoding RNAs at the Ghent University leading to several breakthrough papers in recent years. This research covers a wide area from translational (prognostic signatures, drugable targets, preclinical animal models) towards more fundamental (gene and pathway discovery) all supported by an emerging bioinformatics team. In addition, his team is now integrating zebrafish modelling into ongoing neuroblastoma and leukemia research in order to accelerate novel insights into tumor initiation, cooperative genetic defects and perturbed oncogenic signaling as a prelude to identification of novel drug targets.
Team “Neuroblastoma, a tumor model in oncogenesis & differentiation” Team, Head,
CNRS-UMR CNRS # 8126
Institut Gustave Roussy, Villejuif, France
The aim of the team was to pinpoint genetic determinants of clinical interest regarding all neuroblastoma (NB) stages (from infant stage 4S to to highly aggressive stage 4) . Our team has contributed to the use of MYCN genomic content for clinical management of NB and the detection of epigenetic events such as expression of parental imprinted miRNA for NB risk classification.(see PubMed)