Descrizione del progetto
Uno sguardo più approfondito all’interazione tra cellule cancerose ovariche e microambiente tumorale
La resistenza al trattamento nel cancro delle ovaie è diffusa. Il progetto OVADEX, finanziato dall’UE, ha ipotizzato che essa potrebbe essere determinata da un’interazione metabolica tra il microambiente tumorale e le cellule cancerose ovariche. Una possibilità è che la concorrenza per la serina tra questo microambiente e le cellule del cancro ovarico resistenti al platino potrebbe fungere da mediatore per la resistenza al trattamento. Il progetto sta sviluppando una piattaforma basata su espianti prelevati da pazienti che consentirà lo studio delle interazioni tra il microambiente tumorale e le cellule cancerose. Gli obiettivi sono quelli di esporre tali espianti a terapie convenzionali ed emergenti in modo da definire i cambiamenti metabolici nelle cellule cancerose ovariche e nel microambiente tumorale prima e dopo il trattamento. Verranno individuati i legami tra il metabolismo della serina e la resistenza al trattamento, il che porterà a una migliore comprensione della resistenza al trattamento e alla scoperta di modalità valide per superarla.
Obiettivo
Treatment resistance in ovarian cancer (OC) is common. Recent efforts have identified new treatment approaches with potential to improve its management, but their therapeutic effects are limited due to treatment resistances.
Tumor microenvironment (TME) is emerging as a key contributor to treatment resistance, being the metabolic cross-talk between TME and OC one of the recently proposed mechanisms. The hosting lab has evidence that platinum-resistant OC cells have defects in serine biosynthesis which leads to an enhance uptake of serine. Importantly, exogenous serine is also required for some TME components, suggesting a possible competition for it and affecting their anti-cancer function. Thus, my working hypothesis is that metabolic cross-talk between TME and OC could involve serine metabolism, which could mediate treatment resistance.
Unfortunately, there is a lack of preclinical models of OC that recapitulate TME to study its role. In this regard, the secondment lab developed a new ex vivo platform based on patient-derived explants (PDEs) that allows the study of TME interactions with cancer cells. In OVADEX, I will use PDEs to dissect the role of TME components in treatment response in OC, and particularly, in the metabolic reprogramming of cancer cells. My objectives are to generate OC PDEs and expose them to standard and emerging therapies, to define metabolic changes in OC cells and cellular and phenotypic changes in TME before and after treatment and to associate changes in TME and OC cells to serine metabolism and treatment resistance. To this end, I will integrate innovative techniques and the access of the hosting team to a unique registry of OC patients.
Through this work, I aim to broaden my scientific expertise and my international network for pursuing an academic career in Europe. OVADEX will contribute to actualize many objectives outlined in my career development plan to become a PI in the field of preclinical models for cancer applications.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
3000 Leuven
Belgio