US 2017/0363630 A1Published application

Methods for breast cancer treatment

AssigneeGeorge Mason Research Foundation, Inc.

InventorsEmanuel PETRICOIN, Julia WULFKUHLE

Life of this patent

Estimating the term…

Abstract

Disclosed herein are methods for treating subjects with breast cancer, comprising determining a therapeutic regimen for cancer by measuring the level (amount) of proteins of one or more biomarkers. Also disclosed are methods of predicting or assessing therapeutic outcome for subject.

Claims24

Dependent claims

A method for treating breast cancer regardless of ER, PR and/or HER2 status, comprising, treating a subject identified as having breast cancer with at least one therapeutic agent that targets EGFR and HER2, wherein the efficacy of the at least one therapeutic agent has been determined by a) measuring protein levels of one or more biomarkers in cellular samples from subjects prior to treatment with the therapeutic agent, and b) comparing the measured protein levels of the one or more biomarkers from the subjects to a baseline value for the respective one or more biomarkers, wherein an elevated or decreased level of the proteins of the one or more biomarkers indicates that the subject is a responder to the therapeutic agent, wherein a biomarker is selected from one or more of the following:

ALK.Y1586;
ALK.Y1604;
AMPKb1.S108;
Caspase.7, cleaved D198;
Cyclin.B1 total;
Cyclin.D1.total;
EGFR.Y1068, EGFR.Y1173, EGFR.Y992, eIF4G.S1108;
IGFBP5.total;
ERBB2.total;
ERBB2.Y1248;
ERBB2.Y877;
ERBB3.Y1289;
ERBB4.Y1284;
FAK.Y576.Y577;
JAK1.Y1022 and Y1023;
JAK2.Y1007;
MEK1.2.S217 and S211;
MET.Y1234 and Y1235;
p70S6K.T389;
p70S6K.T412;
PI3K.p85.Y458.p55. and Y199;
AKT S473;
AKT T308;
EGFR total;
EGFR Y1148;
ERBB3 total;
ERK1/2 T202/Y204;
Heregulin total;
mTOR S2448;
mTOR total;
PTEN S380;
SHC Y317;
PARP.total;
PDGFRa.Y754;
RET.Y905;
RTK.ROR1.total;
SHC.Y317;
STAT5.Y694;
VEGFR2.Y996;
X4EBP1.S65;
AMPKa1.S485;
A.RAF.S299;
IGF1R.Y1131. and IR.Y1146;
MCSFR.Y732;
A.RAF.S299;
LC3B.total;
TIE2.Y992;
a JAK.STAT.pathway score (which is the sum of the measurements for JAK1 Y1022/Y1023, JAK1 Y1007, STAT1 Y701 STAT2Y727, STAT3 Y705, STAT5 Y694), a mTOR pathway score (which is the sum of the measurements for 4EBP1 S65;
eIF4E S209;
eIF4G S1108;
eIF4G S1108;
eIF4G S1108;
mTOR S2448;
p70S6K S371;
p70S6K T389;
p70S6K T412;
S6RP S240/S244);
a HER Family pathway score (which is the sum of the measurements for EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
RET Y905);
and a RTK pathway score (which is the sum of the measurements for ALK Y1604;
EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
ERBB2 Y877;
ERBB4 Y1284;
MET Y1234-Y1235;
ROS Y2274;
RET Y905), or combinations thereof.

77 more elements

A method of predicting or assessing an increased likelihood of tumor shrinkage after treatment with a TKI (tyrosine kinase inhibitor) therapeutic agent that targets EGFR and HER2, comprising a) measuring, in a pre-treatment tumor sample comprising cancer cells from a subject, protein levels of one or more biomarkers disclosed herein, b) comparing the measured protein levels of the one or more biomarkers from the subject to a baseline value for the respective protein levels of the one or more biomarkers, wherein an elevated or decreased level of the proteins of the respective one or more biomarkers indicates that the subject has an increased likelihood of tumor shrinkage after treatment with the TKI therapeutic agent, wherein the one or more biomarkers comprise ALK.Y1586;

ALK.Y1604;
AMPKb1.S108;
Caspase.7, cleaved D198;
Cyclin.B1 total;
Cyclin.D1.total;
EGFR.Y1068, EGFR.Y1173, EGFR.Y992, eIF4G.S1108;
IGFBP5.total;
ERBB2.total;
ERBB2.Y1248;
ERBB2.Y877;
ERBB3.Y1289;
ERBB4.Y1284;
FAK.Y576.Y577;
JAK1.Y1022 and Y1023;
JAK2.Y1007;
MEK1.2.S217 and S211;
MET.Y1234 and Y1235;
p70S6K.T389;
p70S6K.T412;
PI3K.p85.Y458.p55. and Y199;
AKT S473;
AKT T308;
EGFR total;
EGFR Y1148;
ERBB3 total;
ERK1/2 T202/Y204;
Heregulin total;
mTOR S2448;
mTOR total;
PTEN S380;
SHC Y317;
PARP.total;
PDGFRa.Y754;
RET.Y905;
RTK.ROR1.total;
SHC.Y317;
STAT5.Y694;
VEGFR2.Y996;
X4EBP1.S65;
AMPKa1.S485;
A.RAF.S299;
IGF1R.Y1131. and IR.Y1146;
MCSFR.Y732;
A.RAF.S299;
LC3B.total;
TIE2.Y992;
a JAK.STAT.pathway score (which is the sum of the measurements for JAK1 Y1022/Y1023, JAK1 Y1007, STAT1 Y701 STAT2Y727, STAT3 Y705, STAT5 Y694), a mTOR pathway score (which is the sum of the measurements for 4EBP1 S65;
eIF4E S209;
eIF4G S1108;
eIF4G S1108;
eIF4G S1108;
mTOR S2448;
p70S6K S371;
p70S6K T389;
p70S6K T412;
S6RP S240/S244);
a HER Family pathway score (which is the sum of the measurements for EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
RET Y905);
and a RTK pathway score (which is the sum of the measurements for ALK Y1604;
EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
ERBB2 Y877;
ERBB4 Y1284;
MET Y1234-Y1235;
ROS Y2274;
RET Y905), or combinations thereof.

76 more elements

A method of treating cancer in a subject, comprising, administering an effective amount of at least one TKI that targets EGFR and HER2, wherein the subject has been identified as having an elevated or decreased level (amount) of proteins of one or more biomarkers, wherein the protein level measured is compared to a baseline value for the proteins of the respective one or more biomarkers, wherein the one or more biomarkers comprise ALK.Y1586;

ALK.Y1604;
AMPKb1.S108;
Caspase.7, cleaved D198;
Cyclin.B1 total;
Cyclin.D1.total;
EGFR.Y1068, EGFR.Y1173, EGFR.Y992, eIF4G.S1108;
IGFBP5.total;
ERBB2.total;
ERBB2.Y1248;
ERBB2.Y877;
ERBB3.Y1289;
ERBB4.Y1284;
FAK.Y576.Y577;
JAK1.Y1022 and Y1023;
JAK2.Y1007;
MEK1.2.S217 and S211;
MET.Y1234 and Y1235;
p70S6K.T389;
p70S6K.T412;
PI3K.p85.Y458.p55. and Y199;
AKT S473;
AKT T308;
EGFR total;
EGFR Y1148;
ERBB3 total;
ERK1/2 T202/Y204;
Heregulin total;
mTOR S2448;
mTOR total;
PTEN S380;
SHC Y317;
PARP.total;
PDGFRa.Y754;
RET.Y905;
RTK.ROR1.total;
SHC.Y317;
STAT5.Y694;
VEGFR2.Y996;
X4EBP1.S65;
AMPKa1.S485;
A.RAF.S299;
IGF1R.Y1131. and IR.Y1146;
MCSFR.Y732;
A.RAF.S299;
LC3B.total;
TIE2.Y992;
a JAK.STAT.pathway score (which is the sum of the measurements for JAK1 Y1022/Y1023, JAK1 Y1007, STAT1 Y701 STAT2Y727, STAT3 Y705, STAT5 Y694), a mTOR pathway score (which is the sum of the measurements for 4EBP1 S65;
eIF4E S209;
eIF4G S1108;
eIF4G S1108;
eIF4G S1108;
mTOR S2448;
p70S6K S371;
p70S6K T389;
p70S6K T412;
S6RP S240/S244);
a HER Family pathway score (which is the sum of the measurements for EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
RET Y905);
and a RTK pathway score (which is the sum of the measurements for ALK Y1604;
EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
ERBB2 Y877;
ERBB4 Y1284;
MET Y1234-Y1235;
ROS Y2274;
RET Y905), or combinations thereof.

76 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/533,859Filed 8 Dec 2015
Priority: 8 Dec 2014
Published: 21 Dec 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

G01N 33/57515
For cancer: of the breast
A61P 35/00
Antineoplastic agents
G01N 2800/52
Detection or diagnosis of diseases: predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in…
G01N 2800/56
Detection or diagnosis of diseases: staging of a disease; Further complications associated with the disease

Family

Application62/089,120Us provisional application · filed 8 Dec 2014
US 10,690,672 B2Related patent
US 2017/0363630 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

ALK.Y1586;
ALK.Y1604;
AMPKb1.S108;
Caspase.7, cleaved D198;
Cyclin.B1 total;
Cyclin.D1.total;
EGFR.Y1068, EGFR.Y1173, EGFR.Y992, eIF4G.S1108;
IGFBP5.total;
ERBB2.total;
ERBB2.Y1248;
ERBB2.Y877;
ERBB3.Y1289;
ERBB4.Y1284;
FAK.Y576.Y577;
JAK1.Y1022 and Y1023;
JAK2.Y1007;
MEK1.2.S217 and S211;
MET.Y1234 and Y1235;
p70S6K.T389;
p70S6K.T412;
PI3K.p85.Y458.p55. and Y199;
AKT S473;
AKT T308;
EGFR total;
EGFR Y1148;
ERBB3 total;
ERK1/2 T202/Y204;
Heregulin total;
mTOR S2448;
mTOR total;
PTEN S380;
SHC Y317;
PARP.total;
PDGFRa.Y754;
RET.Y905;
RTK.ROR1.total;
SHC.Y317;
STAT5.Y694;
VEGFR2.Y996;
X4EBP1.S65;
AMPKa1.S485;
A.RAF.S299;
IGF1R.Y1131. and IR.Y1146;
MCSFR.Y732;
A.RAF.S299;
LC3B.total;
TIE2.Y992;
a JAK.STAT.pathway score (which is the sum of the measurements for JAK1 Y1022/Y1023, JAK1 Y1007, STAT1 Y701 STAT2Y727, STAT3 Y705, STAT5 Y694), a mTOR pathway score (which is the sum of the measurements for 4EBP1 S65;
eIF4E S209;
eIF4G S1108;
eIF4G S1108;
eIF4G S1108;
mTOR S2448;
p70S6K S371;
p70S6K T389;
p70S6K T412;
S6RP S240/S244);
a HER Family pathway score (which is the sum of the measurements for EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
RET Y905);
and a RTK pathway score (which is the sum of the measurements for ALK Y1604;
EGFR Y1068;
EGFR Y1173;
EGFR Y992;
ERBB2 Y1248;
ERBB3 Y1289;
FAK Y576/Y577;
SHC Y317;
STAT5 Y694;
ERBB2 Y877;
ERBB4 Y1284;
MET Y1234-Y1235;
ROS Y2274;
RET Y905), or combinations thereof.

77 more elements

Facts

Application

15/533,859Filed 8 Dec 2015

Priority

8 Dec 2014

Published

21 Dec 2017

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

G01N 33/57515
For cancer: of the breast
A61P 35/00
Antineoplastic agents
G01N 2800/52
Detection or diagnosis of diseases: predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in…
G01N 2800/56
Detection or diagnosis of diseases: staging of a disease; Further complications associated with the disease