Enigma and CDH18 as companion diagnostics for CDK4 inhibitors
The present disclosure relates to the use of one or more biomarkers to evaluate the likelihood that a CDK4 inhibitor would produce an anti-cancer effect in a subject. Accordingly, in certain non-limiting embodiments, the present disclosure provides for methods, compositions and kits for a companion diagnostic for CDK4 inhibitors, and in particular, for the use of the colocalization of Enigma and CDH18 biomarkers to foci within the cancer for determining whether the cancer can be successfully treated by CDK4 inhibition.
1. A method for selecting cancer patients for treatment with a CDK4 inhibitor, comprising
(a) detecting CDH18 protein expression pattern within one or more cancer cells present in samples obtained from cancer patients;
(b) selecting cancer patients in which CDH18 protein is localized to foci within the one or more cancer cells; and
(c) administering an effective amount of a CDK4 inhibitor to the cancer patients of step (b), wherein the cancer is selected from the group consisting of liposarcoma, glioma, non-small cell lung cancer, and breast cancer.
2. The method of claim 1 , wherein CDH18 is detected by immunofluorescence.
3. The method of claim 1 , wherein the cancer is a liposarcoma.
4. The method of claim 1 , wherein the cancer is a glioma.
5. The method of claim 1 , wherein the cancer is a non-small cell lung cancer.
6. The method of claim 1 , wherein the cancer is a breast cancer.
7. A method for treating cancer in cancer patients that have received CDK4 inhibitor therapy, comprising
(a) detecting CDH18 protein expression pattern within one or more cancer cells present in samples obtained from the cancer patients that have received CDK4 inhibitor therapy;
(b) selecting cancer patients in which CDH18 protein is localized to foci within the one or more cancer cells; and
(c) administering an effective amount of a CDK4 inhibitor to the cancer patients of step (b), wherein the cancer is selected from the group consisting of liposarcoma, glioma, non-small cell lung cancer, and breast cancer.
8. The method of claim 7 , wherein the cancer is a liposarcoma.
9. The method of claim 7 , wherein the cancer is a glioma.
10. The method of claim 7 , wherein the cancer is a non-small cell lung cancer.
11. The method of claim 7 , wherein the cancer is a breast cancer.
12. The method of claim 1 , wherein the CDK4 inhibitor is palbociclib, ribociclib, abemaciclib, PD0332991, P1446A-05, trilaciclib, flavopiridol hydrochloride, a CDK4 antisense oligonucleotide, a CDK4 shRNA, or a CDK4 siRNA.
13. The method of claim 7 , wherein the CDK4 inhibitor is palbociclib, ribociclib, abemaciclib, PD0332991, P1446A-05, trilaciclib, flavopiridol hydrochloride, a CDK4 antisense oligonucleotide, a CDK4 shRNA, or a CDK4 siRNA.