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Prostate Cancer UK has awarded nearly £430,000 to Dr Srinivasa Rao and Associate Professor Clare Verrill from the Nuffield Department of Surgical Sciences (NDS) to lead a three-year project investigating why some prostate cancers change shape and become more dangerous, with the aim of helping men with prostate cancer to get the most effective treatment.

Prostate cells from the same patient, showing cribriform transformation on the right. Cribriform pattern prostate cancer has poorer prognosis.
Prostate cells from the same patient, showing cribriform transformation on the right. Cribriform pattern prostate cancer has poorer prognosis.

Using artificial intelligence (AI) to analyse the shapes of cancer cells from men who had prostate surgery, the researchers will study the cells’ genes to find out which genes make the cancer cells change shape. Knowing which genes cause the shape change could help doctors tell how risky the cancer is and choose better treatments. It could also make diagnosing prostate cancer easier and more accurate.

The microscopic examination of prostate glands from cancer patients often reveals diverse shapes, with the cribriform (sieve-like) pattern standing out as a high-risk characteristic. Men with this pattern typically face a more aggressive disease trajectory. However, the cribriform pattern commonly intertwines with other shapes, prompting the research team to delve into understanding the genetic alterations driving the transition from non-cribriform to cribriform shapes.

Dr Rao, the study's Principal Investigator, said: 'Finding a link between the genomic status and microscopic appearance of the tissue will help identify higher risk disease more easily in men with prostate cancer.'

The project's core objective revolves around conducting comprehensive analyses of prostate cancer tissues to explain the genetic changes responsible for this shapeshifting phenomenon. Evolutionary analyses will be employed to identify the molecular steps involved in the transition of cancer cells from one shape to another.

Professor Verrill, Co-Principal Investigator, said: 'We will be using cutting-edge technology and science to unlock new insights which we hope will ultimately be able to be translated into diagnostic pathways and improve outcomes for patients.'

Dr Rao and Professor Verrill's approach aims to achieve two pivotal outcomes:

Firstly, by linking genetic changes with distinct tissue shapes, the study intends to refine risk classification for prostate cancer patients. Identifying genetic changes associated with the cribriform pattern could aid in subclassifying patients, offering tailored prognostic information.

Secondly, certain genetic changes linked to shape shifting may be treatable with existing drugs. Establishing a strong correlation between specific genetic alterations and the emergence of the cribriform pattern could potentially enable predictive diagnosis based solely on tissue morphology, offering a cost-effective and feasible alternative to detect these genetic changes.

The project will integrate tissue shapes, genetic alterations, and clinical data to develop a comprehensive framework, which will then be validated using biopsy samples. While initial validation will focus on improving risk classification, further validation in a larger pool of patient samples will be necessary for potential incorporation into routine diagnostic practices alongside conventional methods such as Gleason Scoring.

The research will primarily utilise archival samples from prostate surgery patients who have consented to contribute to scientific research. Despite potential processing-related defects, the team's specialised methods will facilitate robust genetic analysis. Advanced computational tools will analyse scanned digital slide images to pinpoint specific molecular changes associated with shapeshifting.

The research will benefit significantly from collaboration with Professor Jens Rittscher, Dr Dan Woodcock, Professor Fadi Issa, Dr Willem Bonnaffé, Professor Ian Mills, Professor Claire Edwards, and Professor Freddie Hamdy, collectively contributing invaluable expertise and experience to the project.

Dr Rao added: 'We are in the fortunate position to be able to draw on this wealth of expertise and experience within the department and the University, and we are very keen to get on with this important work.

'As an early career researcher, I am thrilled and grateful to receive this Prostate Cancer UK Research Innovation Award which is a big step on my path to an independent research career.' 

Read more about the project on the Prostate Cancer UK's website