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THE PATHOBIOLOGY OF OVARIAN CANCER
Ovarian cancer (OC) remains an outstanding challenge in clinical oncology, mainly due to the lack of prevention and early diagnosis strategies and the high rate of recurrence and chemoresistance. Experimental and clinical evidence supports the hypothesis that OC relapse and drug resistance are fueled by a subpopulation of ovarian cancer stem cells (OCSC) and, hence, targeting OCSC function may lead to OC eradication. We are pursuing the identification as well as the molecular and functional characterization of OCSC, aimed at defining their biomarkers and possible therapeutic targets.
Another key aspect of OC malignancy is the role of tumor microenvironment, which has emerged as a crucial player and a viable target for new therapies. In this context, the blood vessel network provides an essential support to the growth of primary tumor and metastatic implants. Such a role entails also the establishment of perivascular niches for OCSC. Our group is interested in studying novel biological mechanisms that govern OC-associated vascularization and, in particular, the crosstalk between the vasculature and OCSC. The ultimate objective is the discovery of molecular pathways that can be modulated pharmacologically in order to deprive OC of its vascular support.
Our Unit is fully embedded in the IEO Gynecology Program, and we work in close collaboration with its clinical staff, which not only grants access to patient-derived samples but it also facilitates focusing on clinically relevant questions.
- Recent relevant publications
- Angiolini F., Belloni E., Giordano M., Campioni M., Forneris F., Paronetto M.P., Lupia M., Brandas C., Pradella D., Di Matteo A., Giampietro C., Jodice, G., Luise C., Bertalot G., Freddi S., Malinverno M., Irimia M., Moulton J., Summerton J., Chiapparino A., Ghilardi C., Giavazzi R., Nyqvist D., Gabellini D., Dejana E., Cavallaro U.*, and Ghigna C.* (2019) A Novel L1CAM Isoform with Angiogenic Activity Generated by NOVA2-mediated Alternative Splicing. eLife, 8. pii: e44305. *equal contribution
- Lupia M., Angiolini F., Bertalot G., Freddi S., Sachsenmeier K.F., Chisci E., Kutryb-Zajac B., Confalonieri C., Smolenski R.T., Giovannoni R., Colombo N., Bianchi F., and Cavallaro U. (2018) CD73 regulates stemness and epithelial-mesenchymal transition in ovarian cancer-initiating cells. Stem Cell Reports, 10:1412-1425.
- Francavilla C.*, Lupia M.*, Tsafou K., Villa A., Kowalczyk K., Rakownikow Jersie-Christensen R., Bertalot G., Confalonieri S., Brunak S., Jensen L.J., Cavallaro U.*, Olsen J.V.* (2017) Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer. Cell Rep., 18:3242-3256. *equal contribution
- Magrini E., Villa A., Angiolini F., Doni A., Mazzarol G., Rudini N., Maddaluno L., Komuta M., Topal B., Prenen H., Schachner M., Confalonieri S., Dejana E., Bianchi F., Mazzone M., and Cavallaro U. (2014) Endothelial-specific deficiency of adhesion molecule L1 reduces tumor angiogenesis. J. Clin. Invest., 124:4335-4350.