MSc Srikar Nagelli defends his dissertation in Pathology entitled “CIP2A is a critical DNA damage response protein that drives basal-like breast cancer” at the University of Turku on 14 April 2023 at 12pm (Turku School of Economics, Lähitapiola lecture hall, Rehtorinpellonkatu 3, Turku).

The audience can participate in the defence through remote access.

Opponent: Professor Dipanjan Chowdhury (Harvard Medical School, Boston, USA)
Custos: Professor Jukka Westermarck (University of Turku)

Digital copy of the dissertation at UTUPub

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Summary of the Doctoral Dissertation:

Breast cancer is the leading cause of cancer across the globe. Basal-like breast cancer (BLBC), accounting for 15% of breast cancer cases, is clinically the most challenging breast cancer subtype. Most of the patients of this subtype are of triple-negative type meaning they their cancer cells do not express breast-specific surface receptors estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2). Except for a small proportion of patients that have specific gene mutations, there are no targeted therapies that work for these patients.

This dissertation identifies a novel role for the protein CIP2A as a driver of BLBC tumorigenesis and established its role as a potential BLBC therapy target protein. The work also demonstrated for the first time that CIP2A is an important DNA damage response protein (DDR). CIP2A interacts with TopBP1 and inhibits its recruitment to the DNA-damaged site and thereby allowing the progression of DNA-damaged cells to enter unrepaired, into mitosis.

Secondly, the thesis addresses the important clinical problem that all BLBC patients are treated with aggressive chemotherapy though some of these patients might not require such aggressive treatment and could be spared from the side effects. Also, some patients do not respond well to these chemotherapy drugs, and this could be attributed to poor patient stratification methods. Using RNA sequencing method, a CIP2A gene signature was developed which can predict the aggressivity of breast cancer and could be used to identify drugs and drug combinations that show clinical benefit for the different stratified BLBC subgroups.

Overall, this dissertation reports a new driver mechanism of BLBC that can potentially be therapeutically targeted and identifies a new personalized treatment strategy for better clinical management of BLBC.