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Nov 2017 - Jun 2021

Exploiting DNA repair defects found in cancer cells for treatment with topoisomerase poisons and nucleoside analogues

Student

Martina Salerno

Location

North Wales

Funding Amount

£13,500

Supervisor

Dr Edgar Hartsuiker

Cancer Type

All

Funding Type

PhD

Status

Complete

Research Type

Treatment

This PhD was part funded through the Knowledge and Economy Skills Scholarship 2 Programme which you can find out more about here

Study: Cancer cells can be targeted exploiting their DNA repair defects. In this project, the student has aimed to develop Mre11 small molecules inhibitor to use in cancer therapy. Mre11 is a DNA repair protein that could be promisingly targeted in different type of cancers (MYCN driven neuroblastoma, colorectal and endometrial cancers carrying DNA Polymerase ε exonuclease mutations, and more). Currently known inhibitors of Mre11 are not suitable to be employed clinically, therefore the team has worked on the development of novel and more potent Mre11 small molecule inhibitors.

Results: Through the employment of computational studies and biological assays, novel molecules have been identified as Mre11 inhibitors, showing higher activity compared to the known compounds currently available.
Impact (on cancer patients and their families): The project still requires lots of work, but the potential that it has is high and very promising. The compounds the team is trying to development could be efficiently employed at the clinical level and be used for the treatment of the cancers stated above, and potentially many more.
Next Steps: More biological and chemical assays have to be carried out to improve the activity of the compounds and try to develop a suitable candidate for clinical applications in cancer therapy.

Upon completion of her funding, Martina told us:

“Without Tenovus Cancer Care funding I wouldn’t have been able to join the doctoral program at Bangor University, missing a great opportunity to work on such interesting and motivating project. I loved being able to be part of the current research effort in drug discovery for novel cancer treatments, I hope the findings and results I obtained during my PhD would represent a first step towards the development of a new clinical candidate to use in cancer therapy.”

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