Study of the DNA damage response in prostate tumour cells
Research type
Research Study
Full title
Understanding and targeting the DNA damage response in prostate cancer
IRAS ID
275875
Contact name
Tatjana Stankovic
Contact email
Sponsor organisation
University of Birmingham
Duration of Study in the UK
4 years, 8 months, 10 days
Research summary
The cellular DNA damage response (DDR) consists of a number of specialized cellular pathways which function to maintain the integrity of the genome. As they proliferate, cancer cells exhibit a tendency to develop defects in one or more DDR pathways (1). This can promote the occurrence of genomic mutations, drive proliferation and promote tumour cell survival as well reduce cell death.
We have evidence that a member of the RNase H2 complex, which removes misincorporated nucleotides from the genome, is frequently lost in advanced hormone-resistant metastatic prostate cancer (2). We believe that this is a potential Achilles heel for these tumour cells which can be therapeutically exploited.
Whilst we know that a component of RNase H2 is lost in 30-40% of metastatic hormone-resistant prostate cancer (2), there is little information regarding the frequency of RNase H2 loss in other tumour subgroups. Through this study we intend to generate a large cohort of prostate cancer biopsy samples representing different classifications of prostate cancer. Using these samples we will assess the impact of loss of RNase H2 on prostate cancer progression.
In this research we plan to use viable biopsy material and blood taken from patients with, or suspected of having, prostate cancer to generate prostate cancer organoids (3). The organoids are established using special cell culture techniques that mimics the 3-dimensional structure that these cancer cells attain within the body, which in the presence of adequate external signals provide a more representative model of prostate cancer compared to classical 2D cell culture (4).REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
20/EM/0111
Date of REC Opinion
8 Jun 2020
REC opinion
Further Information Favourable Opinion