Methods and compositions for anti-EGFR treatment
In some embodiments, the present invention provides methods for enhancing the sensitivity of cancer cells to anti-EGFR treatment, wherein the method comprises the introduction of a miR-200 miRNA to the cancer cells. In other embodiments, the present invention provides methods for treating cancer by exposing the cancer cells to an anti-EGFR composition after the above-mentioned enhancement step. In other embodiments, the present invention provides methods for assessing and enhancing the sensitivity of cancer cells to anti-EGFR treatment. In various other embodiments, the present invention provides compositions and expression vectors for practicing the afore-mentioned methods.
1. A method of treating a patient having cancer that is resistant to EGFR treatment using anti-EGFR treatment, said method comprising the steps of administering to cells of said cancer an amount of a miR-200 miRNA that is effective to render said cancer sensitive to anti-EGFR treatment; and treating said patient with an anti-EGFR composition.
2. The method of claim 1 , wherein said miR-200 miRNA is selected from the group consisting of miR-200b and miR-200c.
3. The method of claim 1 , wherein said miR-200 miRNA is administered to said cancer cells by transfecting said cancer cells with said miR-200 miRNA.
4. The method of claim 3 , wherein said miR-200 miRNA is comprised in a nanovector.
5. The method of claim 3 , wherein said transfecting comprises lipofection.
6. The method of claim 1 , wherein said miR-200 miRNA is administered introduced to said cancer cells by a targeted delivery method which comprises the use of a targeting moiety that binds to said cancer cells.
7. The method of claim 6 , wherein said targeting moiety is an antibody.
8. The method of claim 6 , wherein the targeting moiety is an aptamer.
9. The method of claim 6 , wherein the targeting moiety is a dendrimer.
10. The method of claim 1 , wherein said miR-200 miRNA is administered to said cancer cells cancer by means of vector that encodes a nucleotide sequence for said miR-200 microRNA.
11. The method of claim 1 , wherein said anti-EGFR treatment comprises treatment of said cancer cells with an anti-EGFR antibody or a small molecule EGFR tyrosine kinase inhibitor.
12. The method of claim 1 , wherein said patient has a cancer that is selected from the group consisting of bladder cancer, breast cancer, pancreatic cancer, lung cancer, and colon cancer.
13. A method of treating cancer using anti-EGFR treatment, said method comprising measuring the level of a miR-200 miRNA in said cancer cells; administering a miR-200 miRNA to said cancer cells to enhance the sensitivity of said cancer cells to anti-EGFR treatment; and treating said cancer cells with an anti-EGFR composition.
14. The method of claim 13 , wherein said measuring step comprises real-time RT-PCR analysis of the RNA of said cancer cells.
15. The method of claim 13 , wherein said measuring step comprises a measurement of a miR-200 miRNA level in a patient's blood or urine sample.
16. The method of claim 13 , wherein said miR-200 miRNA is selected from the group consisting of miR-200b and miR-200c.