Dissecting the role of tau in ovarian carcinoma pathogenesis and drug resistance

Ovarian cancer is a highly insidious disease because it is generally diagnosed at an advanced stage. In Italy, it affects about 5,000 women each year. This tumor has genetic features consistent with alterations of the tau protein, which in the cell is physically associated with microtubules — structural elements of the cell.

Tau plays an important role in chromosome stability and is involved in the development of neurodegenerative diseases. When tau is altered, the normal functions of DNA and chromosomes may be affected. It has already been demonstrated that tau mutations increase the risk of developing neoplasms, but the role of the tau protein in ovarian cancer remains poorly understood. Tau may influence the sensitivity to drugs used clinically to treat ovarian cancer, such as taxanes, which interfere with microtubules; cisplatin and carboplatin, which act by damaging DNA; and poly(ADP-ribose) polymerase inhibitors, which block an important protein involved in DNA damage repair.

Therefore, the aim of this project is to understand the role of tau in the development of ovarian cancer and in the resistance of this tumor to pharmacological treatment.

The research team involved in the project includes scientists from three Italian IRCCSs: the National Cancer Institute of Milan, the Carlo Besta Neurological Institute, and the Giovanni Paolo II Cancer Institute in Bari. They will employ innovative techniques based on the use of nanoparticles to increase or decrease the cellular levels of tau and its mutated forms.

The experiments will be conducted both in cell lines and in miniature replicas of ovarian tumors (organoids), allowing researchers to correlate protein levels with sensitivity to anticancer drugs. In addition, tau levels will be examined both in tumor biopsies and in patients’ blood samples (liquid biopsies).

The results obtained, in addition to providing insights into the molecular mechanisms linking tau to drug sensitivity, will generate innovative personalized medicine approaches aimed at selecting patients based on the characteristics of the protein.