Claims for Patent: 10,488,416

Summary for Patent: 10,488,416

Title:	Targeting breast cancer therapy based on stromal subtypes and CD146 composition
Abstract:	Methods for targeted breast cancer therapy in a subject based upon evaluating the stromal subtypes and CD146 composition in the adjacent tissue. ER+ breast cancers contain two CAF subtypes defined by CD146 expression. CD146.sup.neg CAFs suppress ER expression in ER+ breast cancer cells, decrease tumor cell sensitivity to estrogen, switch ER proliferation dependency toward EGFR dependency and decrease tumor cell sensitivity to antiendocrine therapy. Conversely, the presence of CD146.sup.pos CAFs enhances ER expression in ER+ breast cancer cells and sustains ER-dependent proliferation and sensitivity to tamoxifen. Co-cultures of CD146.sup.pos CAFs with tamoxifen-resistant breast cancer cells restores sensitivity to tamoxifen. Gene expression profiles of patient breast tumors with predominantly CD146.sup.neg CAFs correlate with inferior clinical response to tamoxifen and worse patient outcomes. CAF composition contributes to treatment response and patient outcomes in ER+ breast cancer, and provide a target for drug development.
Inventor(s):	Brechbuhl; Heather (Commerce City, CO), Kabos; Peter (Greenwood Village, CO)
Assignee:	The Regents of the University of Colorado, a body corporate (Denver, CO)
Application Number:	15/617,709
Patent Claims:	1. A method of treating cancer in a subject comprising the steps of: providing a sample containing stroma from cancerous tissue of the subject; screening the sample to detect the CD146(+)-to-CD146(-) ratio of fibroblasts in the stroma; and administering anti-endocrine therapy to the subject responsive to the detection of a high proportion of CD146(+) fibroblasts in the sample relative to a control. 2. The method according to claim 1 wherein the cancer is breast cancer. 3. The method according to claim 1 wherein the anti-endocrine therapy is provided by administering a compound selected from the group consisting of tamoxifen and fulvestrant. 4. A method of treating cancer in a subject comprising the steps of: providing a sample containing stroma from cancerous tissue of the subject; screening the sample to detect the CD146(+)-to-CD146(-) ratio of fibroblasts in the stroma; and administering a TGF.beta. inhibitor to the subject responsive to the detection of a high proportion of CD146(+) fibroblasts in the sample. 5. The method according to claim 4 wherein the cancer is breast cancer. 6. A method of treating cancer in a subject comprising the steps of: providing a sample containing stroma from cancerous tissue of the subject; screening the sample to detect the CD146(+)-to-CD146(-) ratio of fibroblasts in the stroma; and administering an EGFR inhibitor to the subject responsive to the detection of a high proportion of CD146(-) fibroblasts in the sample relative to a control. 7. The method according to claim 6 wherein the cancer is breast cancer. 8. The method according to claim 6 wherein the EGFR inhibitor is a compound selected from the group consisting of gefitinib, erlotonib, and cetuximab. 9. The method according to claim 1 wherein ratio of CD146(+)-to-CD146(-) is 60% CD146(+) to 40% CD146(-) or a higher CD146(+) percentage. 10. The method according to claim 9 wherein the cancer is breast cancer. 11. The method according to claim 9 wherein the anti-endocrine therapy is provided by administering a compound selected from the group consisting of tamoxifen and fulvestrant. 12. The method according to claim 4 wherein ratio of CD146(+)-CD146(-) is 60% CD146(+) to 40% CD146(-) or a higher CD146(+) percentage. 13. The method according to claim 12 wherein the cancer is breast cancer. 14. The method according to claim 6 wherein ratio of CD146(+)-to-CD146(-) is 20% CD146(+) to 80% CD146(-) or a lower CD146(+) percentage. 15. The method according to claim 14 wherein the cancer is breast cancer. 16. The method according to claim 14 wherein the EGFR inhibitor is a compound selected from the group consisting of gefitinib, erlotonib, and cetuximab.

Details for Patent 10,488,416

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2034-12-10
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2034-12-10