KESS2 PhD in Biosciences: Delineating how oncogenic PI3K/PTEN signalling contributes to prostate ...

Cardiff University
September 11 2017
Position Type
Full Time
Organization Type

Prostate cancer (PCa) is the second major cause of cancer-related deaths in men, accounting for >300,000 deaths/annum worldwide.

Despite high response rates to androgen deprivation therapy (ADT) in advanced PCa patients, nearly all eventually develop progressive, castrate-resistant prostate cancer (CRPC). The mainstay of treatment for lethal CRPC is chemotherapy/ADT, yet survival is poor, emphasising the urgent clinical need to identify novel therapeutic strategies to treat PCa/CRPC.

Owing to the high frequency of oncogenic PI3K signalling in PCa/CRPC and its link to ADT resistance, this pathway is an attractive therapeutic target. Indeed loss of PTEN, a negative regulator of the PI3K pathway, occurs in 50-70% of PCa patients and is an inherent property of CRPC in mice.

Nevertheless, how the PI3K pathway contributes to PCa growth and CRPC transition is not clear. Dr. Pearson has recently discovered that hyperactivation of the PI3K catalytic subunit p110a (encoded by PIK3CA) causes rapid de novo castration resistance in combination with Pten loss, yet single mutants acquire CRPC over time.

This PhD project aims to establish the cooperating genetic events underpinning accelerated CRPC progression in Pik3ca-activated and Pten-deficient mutants, to develop a new ex-vivo platform for prostate cancer preclinical trials, and to identify/test novel therapeutic targets and diagnostic biomarkers.

This project offers a unique opportunity to delineate the molecular basis for CRPC in the context of Pten loss using a combination of clinically relevant transgenic models.

The PhD candidate will also develop a new panel of clinically relevant models to improve our molecular understanding of CRPC, and identify and rapidly test novel therapies. Ultimately, this work will provide critical insights into targeting the PI3K pathway in PCa patients, and has immediate implications for the design of clinical trials.

This job comes from a partnership with Science Magazine and Euraxess