Loading patent…
OwnerSarah Martin, Christopher James Lord +1inventors
InventorsSarah Martin, Christopher James Lord, Alan Ashworth
Estimating the term…
Therapeutic approaches to the treatment of DNA mismatch repair (MMR) deficient cancers are disclosed based on the use of complimentary gene-function and drug screening synthetic lethality approaches for designing therapies for the treatment of cancers where loss of tumour suppressor function has occurred. The work is based on experiments using human MSH2, an integral component of the MMR pathway, and is applicable to other genes in the MMR pathway, and in particular MLH1, MSH6, PMS1 and PMS2. In particular loss of MSH2 is synthetically lethal with inhibition of the DNA polymerase POLβ deficiency of MLH1 is synthetically lethal with DNA polymerase γ (POLG) inhibition.
-27. (canceled)
A method of screening for agents useful in the treatment of a DNA mismatch repair (MMR) pathway deficient cancer, the method employing first and second cell lines, wherein the first cell line is deficient in a component of the DNA mismatch repair (MMR) pathway and the second cell line is proficient for said component of the DNA mismatch repair (MMR) pathway, the method comprising:
The method of claim 25, wherein the cell lines are cancer-derived cell lines.
The method of claim 25, wherein the cell lines are a MMR-deficient murine stem cell line.
-53. (canceled)
A method of treating an individual having a DNA mismatch repair (MMR) deficient cancer, the method comprising administering a therapeutically effective amount of an inhibitor of DNA polymerase POLβ to the individual.
A method of treating an individual having a DNA mismatch repair (MMR) deficient cancer, the method comprising administering a therapeutically effective amount of an inhibitor of DNA polymerase POLβ, DNA polymerase POLy, telomerase transcriptional element integrating factor (TEIF or SCYL1) and/or dihydrofolate reductase (DHFR) to the individual.
-60. (canceled)
Dependencies are inferred from the claim text.