© 2016 Kelly:Feber Lab

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RESEARCH

The Kelly:Feber lab is interested in understanding how genetic and epigenetic alterations affect the development and progression of urological cancers (cancer of the male and female urinary tract system and the male reproductive organs), and how these alterations can be used to improve patient outcomes.

Through understanding how these alterations work we are able to find new ways of identifying cancers early and predicting the way in which cancer will develop and respond to treatment.

All cancers begin when one or more genes in a cell are mutated, or changed. How these changes arise in cancer can take several forms.  At the Kelly:Feber Lab, we look at two types of cancer specific DNA alterations:

  • Genomic alterations – where the DNA in a cell is altered or mutated, stopping the cell for making the a gene properly

  • Epigenomic alterations – these changes do not affect the DNA sequence itself, but affect how and when genes are switched on and off

Our lab is focused on using these cancer specific changes to identify new ways to detect the presence of cancer from easy to acquire body fluids like urine and blood. 

Bladder Cancer

Bladder cancer is one of the most expensive cancers to manage and treat, due to the need for invasive cystoscopy to confirm the presence of cancer. In the UK around 110,000 cystoscopies are performed each year, at a cost to the NHS in the region of £55.39 million. However, only around 10%, or 11,000 people, are actually diagnosed with bladder cancer each year, meaning 90% of patients undergo an unnecessary, invasive, uncomfortable and expensive hospital based procedure.

We have developed a test, called the UroMark, which uses cutting edge technology to detect bladder cancer specific changes in cells collected from urine. The UroMark, utilises a platform known as RainDrop BS-Seq to analyse a large panel of bladder cancer specific epigenetic alterations which accurately discriminate between bladder cancer and normal. We have shown that the test performs with high sensitivity and specificity for the detection of bladder cancer, and similar to the current standard of care cystoscopy. In parallel we have also developed a urine collection kit, which allows a urine sample for testing to be provided at home and sent to our lab in the post.

The UroMark test is a highly sensitive test for bladder cancer. The test is 'non-invasive' which means that it is performed on a urine sample and avoids the traditional technique of having to pass an instrument along the urethra or water pipe to visualise the interior bladder.

The UroMark test is uses the latest technology to analyse over 150 cancer related changes to DNA of cells present in urine. Our results to date show that UroMark can detect bladder cancer with high certainty and is able to differentiate between bladder cancer and non-cancer conditions such as urinary infection.

We have also developed a special urine collection kit, which allows a urine sample for testing to be provided at home and sent to our lab in the post.

Penile Cancer

Penile cancer is a rare malignancy in the developed world, with just over 500 new cases in the UK, and 1,600 in the USA, per year. However, the incidence is much higher in developing countries. Although the human papilloma virus (HPV) is known to contribute to the formation of tumours, little is known about the genetic or epigenetic alterations defining penile cancer (PeCa).

We have performed one of the most comprehensive analysis of the genetic and epigenetic alterations present in penile cancers. This has allowed us to identify novel genetic mutations involved in the development of this disease. We also found that changes in DNA methylation appear more prominent in penile cancer development than genetic alterations.

Furthermore, we have also identified HPV-induced specific epigenetic alterations which are predictive of survival in multiple HPV driven cancers and may have utility as a biomarker for the detection of premalignant disease in HPV driven cancers.

Prostate Cancer

Prostate cancer is the most common cancer in men in Western countries. Diagnosing prostate cancer is challenging and is based mainly on prostate-specific antigen (PSA) levels in serum followed by biopsy. However, PSA, currently the best non-invasive marker, is relatively inaccurate, meaning over two thirds of patients with a raised PSA will undergo biopsy and be found to be cancer free or have no life-threatening cancer. Therefore, a significant proportion of men undergo highly invasive, expensive and unnecessary biopsy to rule out the presence of disease. The aim of our work in prostate cancer is to develop a non-invasive assay, which has the potential to remove the uncertainty surrounding PSA testing and improve both diagnosis and treatment of men with prostate cancer.

 

We have recently received funding from Prostate Cancer UK to develop a non-invasive test to detect the presence of prostate cancer specific epigenetic alterations in blood and urine. Our aim is to develop a test that can accurately presence of prostate cancer and to identify men who are more likely to have aggressive disease. 

Biobanking

We have developed an extensive urology biobank. This collection of samples, including cancer tissues and liquid biopsy (blood and urine), are embedded within our clinical trials and enabling genomic research to be conducted on a high quality bio-repository with links clinical outcomes data.

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