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Speaker: Cristina Mir Pérez, Biomedical Research in Cancer Stem Cells - Vall d'Hebron Institute of Research (VHIR)
Introduction: Drug resistance is the principal limiting factor to achieving good survival rates in patients with cancer. The identification of potential biomarkers for diagnosis and prognostic prediction, as well as the design of new molecular-targeted treatments, will be essential to improving head and neck squamous cell carcinoma (HNSCC) patient outcomes.
Aim: The sensitization of resistant cells and cancer stem cells (CSCs) by inhibiting crucial proteins involved in cancer resistance.
Methods: To characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing HNSCC cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and CSCs. Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells.
Results: On the one hand, SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, being Src activation the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of JHU029-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients.
On the other hand, through a virtual screening, sixteen new SDCBP ligands have been identified as candidates for HNSCC therapy.
Conclusions: Our results reveal that genetic and pharmacological targeting of SDCBP could be a potential therapeutic strategy to effectively eliminate CSCs and CDDP resistant tumors.
CV: After the Biomedicine bachelor degree in the Autonomous University of Barcelona (UAB), Cristina Mir studied the Translational Biomedical Research Master degree in the Vall d'Hebron Research Institute (UAB-VHIR). Currently, she is enrolled in the medicine and translational research PhD programme of the University of Barcelona (UB), with the thesis title "Study of resistance to drugs in Head and neck squamous cell carcinoma (HNSCC)", developed in the Biomedical Research in Cancer Stem Cells group and directed by Dr. Lleonart.
Host: Dr. Matilde Lleonart Pajarin, Biomedical Research in Cancer Stem Cells - Vall d'Hebron Institute of Research (VHIR)
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