Annabell Roberti

My research focuses on developing cyclin-dependent kinase 9 (CDK9) inhibitor-based treatment against prostate cancer in preclinical prostate cancer models.

Prostate cancer (PC) is the most prevalent cancer in men and is one of the main causes of cancer-related deaths. Therefore, an unmet clinical need exists for new effective treatment strategies. When cancer cells develop resistance to anti-androgen therapy, tumour cells continue to drive pro-proliferative gene expression even in the presence of anti-androgens, a process dependent on CDK9. While CDK9 inhibitors are currently being tested in clinical trials for solid tumours, the full extent of cancer cell sensitivity to these inhibitors remains poorly understood.

Our previous data reveal that CDK9 inhibitors activate the innate immune response via viral mimicry in cancer cells (Yalala S. et al., FASEB Journal, 2024). The study demonstrated that CDK9 inhibitors can suppress cancer cell proliferation by enhancing NF-ĸB-dependent pro-inflammatory cytokine expression in response to the accumulation of double stranded RNA (dsRNA) due to increased alternative splicing. Additionally, CDK9 inhibition induces DNA damage in vitro, and the resulting transcriptional signature identifies prostate cancer tumours with high levels of genomic instability. By exploring mechanisms of CDK9 inhibitor resistance in vitro and the characterization of CDK9 inhibitor-induced changes of the tumor and tumor microenvironment in vivo, we aim to identify predictors of resistance and determine promising combination therapy strategies.

After finishing my BSc and MSc in Biomedical Science at the Universität Duisburg-Essen in Germany, I did my DPhil in Molecular Cell Biology in Health and Disease at the Sir William Dunn School of Pathology at the University of Oxford. There, I worked in the Greaves Lab working on identifying FDA-approved kinase inhibitors with novel anti-inflammatory activity in macrophages in vitro and in acute mouse models of inflammation in vivo by targeting NF-ĸB signalling and the NLRP3 inflammasome.