Pedro Durao

My research focuses on investigating resistance mechanisms to cyclin-dependent kinase 9 (CDK9) inhibitors in preclinical prostate cancer models. Prostate cancer (PC) is the most common cancer in men in the United Kingdom, and more effective treatments are urgently needed to manage late-stage disease. In this aggressive form of cancer, 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 data reveals that CDK9 inhibitors trigger an innate immune response via viral mimicry (Yalala S. et al., FASEB Journal, 2024). Through a combination of transcription profiling, ChIP-seq, and proteomics, we demonstrate that CDK9 inhibitors suppress the transcription of most genes while enabling the expression of pro-inflammatory cytokines. 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 resistance and sensitivity in vivo, we aim to identify biomarkers that predict treatment responses and propose optimal combination therapy strategies.

I have done my undergraduate studies and master degree in Portugal and then decided to dive into cancer research by doing a PhD in Cancer Research UK Manchester Institute looking at the role of ultraviolet radiation in cancer development and immunotherapy response.