Cisplatin is used to treat a wide variety of tumours in addition to ovarian cancer including, testicular, head and neck and non-small cell lung cancer. In addition, it forms the basis of most combined treatment regimes (where 2 or more drugs are used in combination). The downside to cisplatin is that it is extremely toxic and although some patients benefit substantially from treatment, a large proportion suffer the toxic side effects without any therapeutic benefit. We are aiming to develop a personal test to determine if cisplatin is likely to be effective for an individual’s ovarian cancer, so that the toxic side effects can be avoided if the drug is not going to work.
Nucleotide excision repair (NER) is the biological process that recognises a cell’s DNA has been damaged by cisplatin. For many years the NER proteins have been studied in ovarian cancer response to or resistance to cisplatin. Despite the consistent findings that high or low levels of some NER proteins can predict the effectiveness of cisplatin and cisplatin resistance, the translation of these findings into the clinical setting has not happened. We know what to test and how to test it, but currently clinicians do not use it in the decision process for treating ovarian cancer.
We would like to measure the NER proteins in 500 ovarian cancers where we have the information on wether or not each tumour responded to cisplatin and if it developed resistance. Once we replicate the same results as previous studies, we will have the evidence needed to move onto testing ovarian tumours before the individual receives treatment. By measuring the NER proteins before treatment we will be able to inform the Clinicians if a tumour will or will not respond to cisplatin and if it is likely to develop drug resistance. This will mean toxic chemotherapy treatment will only be given if it has been predicted to be effective. If it is predicted to be non-effective, the patient will not receive chemotherapy and will avoid the unnecessary toxic side effects.