Method of treatment of breast cancers over-expressing the SHP2 signature genes

• US 9,181,553 B2
• Filed: 06/05/2012
• Issued: 11/10/2015
• Est. Priority Date: 06/06/2011
• Status: Active Grant

• Current Assignee: Novartis Forschungsstiftung Zweigniederlassung Friedrich Miescher Institute For Biomedical Research
• Original Assignee: Novartis Forschungsstiftung Zweigniederlassung Friedrich Miescher Institute For Biomedical Research
• Inventors: Aceto, Nicola, Stadler, Michael, Bentires-Alj, Mohamed
• Primary Examiner(s): STOICA, ELLY GERALD
• Application Number:
  US14/124,441
• Publication Number:
  US 20140134184A1
• Time in Patent Office: 1,253 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2310/531 Stem-loop; Hairpin
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Y 301/03048 Protein-tyrosine-phosphatase (3.1.3.48)

Abstract

A method for treating breast cancer in a subject having a breast cancer over-expressing the “SHP2 signature” genes, as compared to normal breast tissue samples, which method comprises the step of administering to said subject a therapeutically effective amount of a modulator of the protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene or of its gene product (Shp2).

Claims

1. A method for treating breast cancer in a subject in need thereof having a breast cancer over-expressing the “

SHP2 signature”

genes, as compared to normal breast tissue samples, which method comprises the steps of;

determining the SHP2 signature gene expression profile in said subject; and

administering to said subject a therapeutically effective amount of a modulator of the protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene or of its gene product (Shp2) (SEQ ID NO;

     1), wherein said modulator is administered to a subject that has overexpression of a SHP2 signature gene or genes compared to normal breast tissue samples; and

wherein said “

SHP2 signature”

genes consist of the genes SGCB, ZSCAN12, ID4, ZIC3, CPVL, HLA-A, MCOLN3, SPATA18, TMEM45A, GNAL, CYBRD1, TSPAN7, ZEB1, CNTLN, NEFL, CENPV, ARL6, HPRT1, LRRC34, PDPN, BEND7, SLC16A10, FAM27E1, PLEKHA1, HERC5, CHIC1, PHF6, ELOVL4, ANTXR1, PRAME, SCML1, CLIP4, CECR2, CNOT10, IGF2BP3, NAP1L3, GPC3, KIAA1804, DGKE, FAS, EPHA6, KDELC1, CRISPLD1, DOCK3, ACSL4, CNTNAP3, PLEKHM3, RDX, TBX18, RRAGD, HOXB5, SNCA, FUNDC2, ITGA8, HFM1, IGF2BP2, CCND2, SGTB, MKX, CRYBG3, WBP5, LPHN3, BEX4, CPNE8, GLDC, SLC35F1, HOXA13, SERPINF1, NEFM, SYCP2L, FHL1, APOBEC3C, CALD1, FKBP10, HOXD11, DENND2C, LRRC49, FAM55C, KIAA0408, HOXB9, C160RF62, ACN9, TUSC3, ELOVL2, SPOCK3, HOXB6, WDR35, MPP1, FBXO38, PRKAA2, SLAIN1, NPHP3, KIAA1524, PRPS1, GJC1, AMOT, SLC9A6, KCTD12, NUP62CL, DZIP3, JAM3, HOXA9, ANKRD19, CDKN2A, BCAT1, OAT, LPHN2, CCDC82, HSD17B11, SAMHD1, WDR17, STK33, GSTP1, TRPC1, CKB, LIN28B, ALDH1L2, SACS, CLGN, MYO3A, EPB41L3, SLC25A27, VCAN, GPX8, GALNT13, PVRL3, MOXD1, HEY1, MAP7D3, ESD, MPP6, EYA4, SPG20, ZDBF2, ZNF204, IFT57, AKR1B1, ADAT2, ZNF717, CCDC88A, ZNF215, MID1, FBN2, LOC100130876, TCEAL8, IGF2BP1, ANKRD18B, PLAGL1, PM20D2, LDHB, C15ORF51, PTPN11, EPB41L2, TLE4, GOLM1, C6ORF192, HOXD13, SLIT2, UCHL1, DYNC2H1, CPS1, GPR180, PYGL, NRN1, PRTFDC1, SLC16A1, DSC3, TMCO1, LRCH2, SLC6A15, DZIP1, HOXA5, HSPA4L, CDR1, PLS3, ECHDC1, SMARCA1, CXORF57, HOXD10, and IRS4.

2. The method of claim 1, wherein an inhibitor decreases or silences the expression of PTPN11.

3. The method of claim 1 wherein the subject is a mammal.

4. The method of claim 1, wherein the modulator is administered to the subject before, during or after radiation therapy, chemotherapy targeted therapy or after surgical removal of a primary tumor.

5. The method of claim 1, wherein the cancer is a solid tumor.

6. The method of claim 1, wherein metastasing of a primary tumor is inhibited.