DNA damage response deficiency assay validation (version 1)
Research type
Research Study
Full title
Clinical and analytical validation of a diagnostic assay to predict response to DNA damaging chemotherapy in breast and gastrointestinal cancers.
IRAS ID
190657
Contact name
Joy Kavanagh
Contact email
Sponsor organisation
Almac
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
The purpose of this research is to clinically and analytically validate the Almac DNA damage response deficiency (DDRD) assay, a microarray based gene expression signature, which may have predictive value in both breast and gastrointestinal (GI) cancers (including oesophageal adenocarcinoma and colorectal cancer). This signature identifies a subgroup of patients whose tumours are more sensitive to DNA damaging chemotherapies and who will gain the most benefit from the current chemotherapy treatment regimens.
The DDRD assay was initially developed in breast cancer to prospectively identify patients most likely to benefit from standard of care anthracycline-based chemotherapy and was further validated in a publicly available independent cohort of 203 patients. The results of this study showed that the DDRD assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide). In addition, samples from an independent cohort of breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide were profiled at Almac using the DDRD assay. A DDRD positive result was able to predicted 5-year relapse-free survival, compared with the assay negative population.
Clinical use of the DDRD assay would enable clinicians to prescribe specific DNA damaging therapies only to those cancer patients who would be likely to respond to treatment. Any patients predicted to be unresponsive to the DNA damaging agent would then be recommended for more appropriate therapies. The main advantage of this would be patient avoidance of unnecessary exposure to potentially toxic treatment, leading to an improved quality of life.
The outcome of this study will be a validated diagnostic assay that can be used to stratify breast and gastrointestinal cancer patients for treatment with DNA damaging chemotherapy.
REC name
London - Chelsea Research Ethics Committee
REC reference
15/LO/1930
Date of REC Opinion
29 Oct 2015
REC opinion
Favourable Opinion