What is the project scope?
Many people suffer from Triple Negative Breast Cancer (TNBC) and at present treatment fo this is not effective. However, it has recently been discovered that Checkpoint Kinase 1 (CHK1), a serine/threonine kinase activated in response to DNA damage, which can be caused by conventional chemotherapy treatments may play a role in this particular cancer. A number of CHK1 inhibitors are currently in clinical development. This includes CCT245737, a potent, selective, orally bioavailable inhibitor of CHK1
It is suggested that CHK1 inhibition may be effective as a monotherapy for some patients. The plan is to test out this suggestion.
Working in conjunction with clinicians at the Kent Oncology Centre, a Multi Disciplinary Team with the School of Biosciences at the University of Kent has been formed to work through the following questions:
1 The TNBC cell lines available that are resistant to the cell lines available form the Resistant Cancer Cell Line (please see the project report on this) will be investigated.
2 Using the data available from that analysis, biomarkers will be identified.
3 These biomarkers will be validated against TNBC samples from the Kent Oncology Centre.
Following this work, it should be possible to decide whether there is scope for a more detailed project to develop a useful drug to provide improved treatment of this form of breast cancer that currently affects some 90 patients through the Kent Oncology Centre at Maidstone each year.
What will this cost?
£15,000 will be spent over 3 years to provide the supplies that the PhD candidate working on this will require. The salary and teaching costs of the PhD candidate will be met from a different source.
PROJECT UPDATE - June 2017
Helen Grimsley, who is partly funded by Kent Cancer Trust, has been working on the Triple Negative Breast Cancer project in order to gain a PhD, since September 2016. She gave a fascinating desciption of what has been achieved in her first year in June 2017. In particular, she talked about the way in which her work has been helped by the ready availability of the Resistant Cancer Cell Line that is kept at the University of Kent
To date, she has characterised a panel of 18 triple-negative breast cancer cell lines (3 parental cell lines, 15 drug-adapted sub-lines) for sensitivity to a panel of anti-cancer drugs. In addition, the University of Kent has acquired the whole exome sequencing data for these cell lines (i.e. they know the sequences of all genes in the genome of these cell lines). These data will be used to identify potential markers of resistance formation to inform anti-cancer therapies. If the changes that indicate resistance formation are known, the resistance formation can be monitored more closely in patients and hence spare them from a therapy that has stopped working. This will become more and more relevant with the use of liquid biopsies (e.g. circulating tumour DNA and circulating tumour cells that can be obtained from patients’ blood and indicate changes in the cancer cells of a patient). In addition, the combination of the drug sensitivity data and the genetic information can be used to indicate effective next-line therapies.
PROJECT UPDATE - May 2019
Helen Grimsley has continued her work as a PhD student on the Triple Negative Breast Cancer project in the School of Biosciences at the University of Kent.
In our previous project update, we reported that Helen had evaluated 18 triple negative breast cancers for sensitivity to a large panel of anti-cancer drugs. Analysis of the DNA sequences of these cell lines has shown differences in the DNA mutations found in the drug resistant versus parental cells. Helen has analysed the DNA mutation data, and by combining it with the drug evaluation data she previously generated, has identified candidate biomarkers of drug resistance. These biomarkers have the potential to be used to indicate the emergence of drug resistance in a patient’s tumour and inform clinicians that a treatment change may be necessary as early as possible. The biomarkers could also indicate effective next-line therapies.
Helen will use the rest of her time on her PhD project validating these candidate biomarkers, to determine whether they could be used in this way to aid in the treatment of triple negative breast cancer patients.