Compositions and methods for treating breast cancer
The present disclosure relates to methods and compositions for the treatment of cancer (e.g., breast cancer).
1 . A method of treating breast cancer in a subject in need thereof, comprising conjointly administering an inhibitor of insulin receptor (IR) and an immune checkpoint inhibitor to the subject, wherein the breast cancer is triple negative breast cancer.
2 . The method of claim 1 , wherein the method further comprises conjointly administering an inhibitor of insulin-like growth factor 1 receptor (IGF1R) to the subject.
3 . The method of claim 2 , wherein the inhibitor of IGF1R is selected from dalotuzumab, MK-2206, ridaforolimus, MK-0752, NVP-AEW541, cetuximab, irinotecan, cisplatin, etoposide, figitumumab, carboplatin, paclitaxel, dexamethasone, docetaxel, prednisone, everolimus, ganitumab, exemestane, fulvestrant, folfiri, gemcitabine, panitumumab, sorafenib, linsitinib, R1507, and BMS-754807 or a pharmaceutically acceptable salt thereof; or a combination of any of the foregoing.
4 . The method of claim 2 , wherein the inhibitor of IGF1R is BMS-754807.
5 . The method of claim 1 , wherein the inhibitor of IR is selected from linsitinib, ceritinib, BMS-754807, S961 TFA, S961, BMS-536924, NVP-AEW541, AGL-2263, GSK1838705A, NVP-TAE 226, AG1024, MSDC 0160, NVP-ADW742, kaempferitrin, rhoifolin, and KU14R or a pharmaceutically acceptable salt thereof.
6 . The method of claim 1 , wherein the inhibitor of IR is BMS-754807.
7 . The method of claim 1 , wherein the immune checkpoint inhibitor is an inhibitor of CD27, CD28, CD80, CD86, CD40, CD122, CD137, OX40, GITR, ICOS, A2AR, B7-HR, BTLA, CTLA-4, IDO, KIR, LAG3, NOX2, PD-1, PD-L1, PD-L2, TIM-3, VISTA, or SIGLEC7.
8 . The method of claim 1 , wherein the immune checkpoint inhibitor is an inhibitor of PD-L1.
9 . The method of claim 1 , wherein the immune checkpoint inhibitor is an antibody or a small molecule.
10 . The method of claim 9 , wherein the immune checkpoint inhibitor is a polyclonal antibody, an intact monoclonal antibody, an antibody fragment, a single chain Fv (scFv), a chimeric antibody, a humanized antibody, or a fusion protein.
11 . The method of claim 1 , wherein the immune checkpoint inhibitor is selected from anti-CD274/B7-H1/PD-L1 clone 10F.9G2, atezolizumab, avelumab, cemiplimab, durvalumab, nivolumab, pembrolizumab, KB035, CK-301, AUNP12, CA-170, and BMS-986189 or a pharmaceutically acceptable salt thereof.
12 . The method of claim 1 , wherein the method further comprises conjointly administering an androgen receptor (AR) antagonist to the subject.
13 . The method of claim 12 , wherein the AR antagonist is selected from 17α-hydroxyprogesterone, chlormadinone acetate, cyproterone acetate, megestrol acetate, osaterone acetrate, 19-norprogesterone, nomegestrol acetate, 10-nortestosterone, dienogest, oxendolone, 17α-spirolactone, drospirenone, spironolactone, medrogestone, bicalutamide, flutamide, nilutamide, apalutamide, darolutamide, enzalutamide, proxalutamide, cimetidine, and topilutamide or a pharmaceutically acceptable salt thereof.
14 . The method of claim 12 , wherein the AR antagonist is enzalutamide or a pharmaceutically acceptable salt thereof.
15 . The method of claim 1 , wherein the breast cancer is quadruple negative breast cancer.
16 . The method of claim 1 , wherein the triple negative breast cancer is relapsed or refractory.
17 . The method of claim 1 , wherein the subject is a woman.
18 . The method of claim 1 , wherein the triple negative breast cancer is metastatic.
19 . The method of claim 1 , wherein the subject has a familial history of breast cancer.