Precision oncology in ovarian cancer

The Wnt pathway is a complex signaling cascade that is involved in the regulation of cell growth, differentiation, and survival. Canonical Wnt pathway, also known as the β-catenin-dependent pathway, controls cell proliferation, differentiation, and survival. The non-canonical Wnt signaling, also known as the β-catenin-independent pathway, plays important roles in cell migration, cell polarity, cytoskeletal organization, and cell fate determination.

ROR1/ROR2 and PTK7 are also known as Wnt-binding receptor pseudokinases. They are called pseudokinases because, although they contain kinase domains, they lack the catalytic activity of traditional protein kinases. Instead, they act as scaffold proteins that can recruit and activate other signaling proteins. It has been shown that ROR1 and ROR2 are overexpressed in several types of cancer and are considered as potential therapeutic targets for cancer treatment. Studies have shown that targeting ROR1 and ROR2 can inhibit cancer cell migration and invasion, and reduce the tumorigenicity of cancer cells by inhibiting the non-canonical Wnt signaling pathway. Both ROR1 and ROR2 have been shown to play a role in the regulation of cancer stem cells (CSCs) by activating the non-canonical Wnt signaling pathway to promote self-renewal, proliferation, survival and drug resistance.

Our research focuses on the molecular mechanisms employed by Wnt-binding receptor pseudokinases such as ROR1, ROR2 and PTK7 to promote cell growth and differentiation. We are interested to understand how these receptors signal and how their dysregulated activation leads to tumor development.

Drug resistance is one of the most challenging problem facing cancer treatments today. The intrinsic drug resistance can occur when cancer cells undergo molecular changes that make them insensitive to a particular drug before treatment even begins. In cases of acquired resistance, cancer cells may adapt to the drug while it is being administered, acquiring molecular changes that allow them to escape its effects. The molecular mechanisms that contribute to drug resistance include mutation of the drug's molecular target, changes in the way the drug interacts with the tumor, broad cellular changes, and changes in the tumor microenvironment, among others.

Another research area of high interest for us is to understand how cancer cells respond to drug treatments at single cell level. We aim to uncover cell-specific gene expression signatures that could provide more insights into drug response mechanisms and advance the power of precision oncology.