Methods for treating cancer resistant to ErbB therapeutics
Provided herein are methods for treating cancer that is resistant to treatment with an anti-ErbB therapeutic agent and which is associated with an activating MET gene mutation or a MET gene amplification. The methods involve administering to a subject a combination of an anti-ErbB therapeutic and an anti-MET therapeutic. Also provided are methods for reducing ErbB mediated signaling or PI3 kinase mediated signaling in a cancer cell.
1. A method for treating non-small cell lung cancer (NSCLC) or gastric cancer in a patient with an acquired resistance to treatment with an anti-ErbB therapeutic, comprising the steps of:
a) selecting a patient with NSCLC or gastric cancer associated with an ErbB activating mutation or an ErbB gene amplification who has developed a resistance to treatment with an anti-ErbB therapeutic, and whose cancer cells comprise cells with a MET activating mutation or a MET gene amplification that reduces downregulation of PI3K/Akt signaling in response to the anti-ErbB therapeutic, and
b) administering to said patient an anti-ErbB therapeutic and an anti-MET therapeutic.
2. The method of claim 1 , wherein the subject has an EGFR, ErbB2, ErbB3, or ErbB4 activating mutation or gene amplification.
3. The method of claim 2 , wherein the subject has an EGFR activating mutation or an EGFR gene amplification.
4. The method of claim 1 , wherein the cancer is resistant to treatment with one or more of the following anti-ErbB therapeutics: an anti-EGFR therapeutic, an anti-ErbB2 therapeutic, an anti-ErbB3 therapeutic, or an anti-ErbB4 therapeutic.
5. The method of claim 1 , wherein the cancer is resistant to treatment with one or more of the following anti-ErbB therapeutics: a small molecule therapeutic, a nucleic acid therapeutic, or a protein therapeutic.
6. The method of claim 5 , wherein the cancer is resistant to treatment with an anti-ErbB antibody.
7. The method of claim 5 , wherein the cancer is resistant to treatment with an ErbB kinase inhibitor.
8. The method of claim 5 , wherein the cancer is resistant to treatment with an EGFR kinase inhibitor.
9. The method of claim 1 , wherein the anti-ErbB therapeutic is selected from the group consisting of gefitinib, erlotinib, lapatinib, PF00299804, CI-1033, EKB-569, BIBW2992, ZD6474, AV-412, EXEL-7647, HKI-272, cetuximab, pantinumumab, and trastuzumab.
10. The method of claim 1 , wherein the anti-MET therapeutic is selected from the group consisting of PHA-665,752, SU11274, SU5416, PF-02341066, XL-880, MGCD265, XL184, ARQ 197, P-470, SGX-523, JNJ38877605, AMG 102, and OA-5D5.
11. The method of claim 1 , wherein:
a) the anti-ErbB therapeutic is selected from the group consisting of gefitinib, erlotinib, lapatinib, PF00299804, CI-1033, EKB-569, BIBW2992, ZD6474, AV-412, EXEL-7647, HKI-272, cetuximab, pantinumumab, and trastuzumab; and
b) the anti-MET therapeutic is selected from the group consisting of PHA-665,752, SU11274, SU5416, PF-02341066, XL-880, MGCD265, XL184, ARQ 197, P-470, SGX-523, JNJ38877605, AMG 102, and OA-5D5.
12. The method of claim 1 , wherein the anti-ErbB therapeutic is gefitinib and the anti-MET therapeutic is PHA-665,752.