We are the combination of four hospitals: the General Hospital, the Children’s Hospital, the Women’s Hospital and the Traumatology, Rehabilitation and Burns Hospital. We are part of the Vall d’Hebron Barcelona Hospital Campus: a world-leading health park where healthcare plays a crucial role.
Below we will list the departments and units that form part of Vall d’Hebron Hospital and the main diseases that we treat. We will also make recommendations based on advice backed up by scientific evidence that has been shown to be effective in guaranteeing well-being and quality of life.
Vols saber com serà la teva estada a l’Hospital Universitari Vall d’Hebron? Aquí trobaràs tota la informació.
Speaker: Dr. Patricia Zarzosa Martínez is a post-doctoral researcher in the Sarcoma laboratory of the Childhood Cancer and Blood Disorders (VHIR)
ABSTRACT: Hedgehog (Hh) signalling exerts an oncogenic role in many cancers. Aberrant activation mechanisms include ligand-dependent, ligand-independent, and non-canonical activation. The only Hh inhibitors approved in clinics target SMO and are effective in ligand-independent Hh tumours. Despite their promising therapeutic potential, Hh inhibitors have not fulfilled clinical expectations in other Hh-associated tumours. Therefore, the therapeutic hopes for effectively targeting the pathway lie in expanding biological knowledge to identify new therapeutic targets. On this premise, our group was the first to describe the aberrant Hh ligand-dependent activation in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in childhood and one of the leading causes of death from infant cancer. Little is known about the Hh co-receptors (BOC and CDO) in cancer, but given their importance for complete autocrine Hh activation and muscle differentiation, we hypothesized a possible oncogenic role in RMS. Our most relevant results are as follows: CDO constitutes a new molecular target of the Hh pathway with high therapeutic potential in RMS. Our results reveal a prominent oncogenic role of CDO in RMS. Besides being overexpressed in cell lines and tumours, CDO is essential for their growth and survival both in vitro and in vivo. Molecularly, CDO regulates the expression levels of the lesser-known Hh pathway transcription factor GLI3. Which we found to be the most highly expressed Hh pathway effector in rhabdomyosarcoma. We co-developed the first experimental anti-CDO compound, named STL-0463. It recapitulates the molecular and functional effects of genetic inhibition of CDO. Concretely, it down-regulates GLI3, causes cell cycle arrest, induction of apoptosis, cell differentiation, and reduction of the invasive capacity of RMS cells. Moreover, it has greater anti-proliferative potency than the reference Hh inhibitors (Vismodegib and Sonidegib) in vitro. Although our compound needs to improve its biodistribution properties, it proves the druggability of CDO and constitutes the first prototype of what could be a successful new therapeutic strategy. CV: Patricia Zarzosa Martínez is a post-doctoral researcher in the Sarcoma laboratory of the Childhood Cancer and Blood Disorders group led by Dr. Josep Roma. She graduated in Biotechnology (BSc, UVIC), specialized in Translational Biomedical Research (MSc, VHIR), and recently obtained her PhD in Biochemistry, Molecular Biology, and Biomedicine (PhD, UAB).
Host: Dr. Josep Roma, Main researcher Childhood Cancer and Blood Disorders (VHIR)
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