Affiliations: UNIL, Stanford University (Oro’s laboratory)
The laboratory is interested in understanding the molecular determinants sustaining basal cell carcinoma (BCC) progression. During the last years, the laboratory identified:
The role of the extracellular microenvironment in BCC progression. Based on their clinical and histological characteristics, thick BCC are typically divided into low-risk nodular and high-risk infiltrative subtypes, although the underlying mechanisms are poorly understood. We identified molecular mechanisms that explain the aggressiveness of high-risk infiltrative BCC, with a potential direct clinical impact. We showed that peritumoral fibronectin promotes adhesion and migration of BCC cells through integrin α5β1-mediated phosphorylation of focal adhesion kinase. Fittingly, both inhibition of integrin α5β1 and phospho-focal adhesion kinase prevent fibronectin-induced migration of BCC cells. Our work open important insights into the pathogenesis of aggressive infiltrative BCC and identify integrin α5β1 or focal adhesion kinase inhibition as promising strategies for the treatment of advanced BCC.
Pathway switching as a mechanism of resistance to Hedgehog (HH) inhibitors. Previous data reported squamous cell carcinoma (SCC) emerging from BCC treated with HH inhibitors. Using high-throughput sequencing, we revealed resistant BCC with a low HH pathway signature and concomitant Ras/MAPK pathway activation. This observation of reduced activation of the HH pathway in resistant BCC contradicts previous demonstration that BCC uniformly depend on the HH pathway for growth. Interestingly, driving constitutively active Ras in HH-responsive cell lines conferred resistance to HH pathway inhibitors, while conferring sensitivity to MAPK inhibitors. Altogether, our results provide new insights into the pathogenesis of resistant BCC and identify the HH to Ras/MAPK pathway switching as a new mechanism of resistance.
In addition, the laboratory is interested in clinical approaches to improve detection and therapy of skin tumors, with a particular focus on dermatologic surgery.
Link to publications