Project No. 05

PTEN: Finding the off switch

Investigating the genetics behind the growth and spread of prostate cancer

S c r o l l   R i g h t

What could this achieve?

This project aims to understand the underlying genetics driving the growth and spread of prostate cancer. This understanding could eventually be used to identify new ways to treat prostate cancer.

How?

Dr de la Rosa has created a new genetic tool which can alter many genes at once. He will explore what happens when the tumour suppressor gene PTEN is lost, and how various genetic changes inside the cell work together to drive prostate cancer.

The Future- what’s next?

Dr de la Rosa will use his genetic tool to generate hundreds of loss-of-function mutations in the mouse prostate and they hope to eventually reveal the genetic weaknesses of prostate cancer cells to identify new therapeutic targets.

What could this achieve?

This project aims to understand the underlying genetics driving the growth and spread of prostate cancer. This understanding could eventually be used to identify new ways to treat prostate cancer.

How?

Dr de la Rosa has created a new genetic tool which can alter many genes at once. He will explore what happens when the tumour suppressor gene PTEN is lost, and how various genetic changes inside the cell work together to drive prostate cancer.

The Future- what’s next?

Dr de la Rosa will use his genetic tool to generate hundreds of loss-of-function mutations in the mouse prostate and they hope to eventually reveal the genetic weaknesses of prostate cancer cells to identify new therapeutic targets.

Project Start

November 2019

Research Facility

University of Cambridge

Budget

£100,000/year

End

November 2020

The Problem With Genetics

There are two types of gene that are important in cancer: oncogenes which are like ‘on switches’ and tumour suppressor genes which are like ‘off switches’. The oncogenes tell cells to grow and make more copies of themselves. The tumour suppressor genes tell cells to stop growing and dividing, preventing cancer in healthy cells. These switches trigger chain reactions and exist as part of a complicated network, like the switches in a fuse box. When a normal cell turns into a cancer cell, it can sometimes be hard to work out which switch has tripped.

The Mystery of PTEN

PTEN is an ‘off switch’ which doesn’t work properly in almost half of advanced prostate cancers.  Despite this, we still don’t know the best way to target these cancers due to the complicated network of genetic ‘switches’. Cancer is a very complex disease and PTEN is not working alone.

Very little is known about the other changes that happen at the same time that PTEN is lost. Science is currently identifying genetic changes much more quickly than we can work out what these genetic changes do. Therefore, we don’t understand how PTEN loss and other changes or ‘switches’ inside the cell work together to drive the growth and spread of prostate cancer.

WHAT WILL THIS MEAN FOR PROSTATE CANCER PATIENTS?

Jorge is identifying the genes that normally stop PTEN-deficient prostate cancers from spreading. He aims to understand how and why changes to these genes lead to the spread of prostate cancer. These genes could be used to diagnose the severity of the disease and decide on the best treatment options for patients. For example, some gene changes may only be found in advanced prostate cancer tumours. Identifying these changes in patients could establish which patients need immediate treatment and which patients can avoid unnecessary treatment.

Jorge will also search for genetic weaknesses of these cancers: genes that prostate cancer cells need to survive but healthy cells don’t. This will then tell him which genes could be targeted by new treatments to attack prostate cancer cells without harming healthy cells. These treatments could eventually lead to better outcomes for patients with advanced prostate cancer.

Jorge's Research Project

 

Jorge will create a new in vivo genetic tool which can be used to alter hundreds if not thousands of genes at once. This tool will be used to identify the other genetic changes that occur when PTEN is lost. Once these changes have been identified, Jorge will explore what they do and how they work with a faulty PTEN to drive prostate cancer.

 

A model system will also be developed as part of Jorge’s research. This model system will imitate the complicated genetic networks behind prostate cancer much better than previous models. This means it can used to test new treatments for prostate cancer patients and identify those that are more likely to be effective with less side effects.

The Future

This project is still in the early stages and Jorge is currently developing his genetic tool. However, he hopes that his project will reveal the genetic changes that lead to advanced prostate cancer. These results can then be used to develop safer and more effective treatments for the disease.

Collaborations and Partnerships

Jorge will be collaborating with a variety of researchers from different institutions across Europe in order to bring his research to fruition. He will be working with scientists from the University of Munich, the University of Oxford, the Wellcome Sanger Institute and the University Central Hospital of Asturias in Spain.

“We aim to identify and understand the faulty genes that cause human prostate tumours to spread, and eventually find the “vulnerabilities” of these disseminated cancers. I am very grateful to PCRC and I feel very excited about this work, which I hope will bring new prognostic and therapeutic opportunities for people with prostate cancer.”

Dr Jorge de la Rosa
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