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Table 7 Characteristic subtype-specific therapeutic vulnerabilities in TNBC

From: Heterogeneity of triple negative breast cancer: Current advances in subtyping and treatment implications

TNBC subtype Pathway Genetic dependency Pharmacologic dependency Patient-derived tumor xenograft dependency
Luminal androgen receptor AR signalling AR
SPDEF
FOXA1
Bicalutamide (AR) Bicalutamide (AR)
PI3K/AKT signalling PIK3CA
AKT1
EIF4A2
RPS6
ERBB2
GSK690693 (AKT)
ZSTK474 (PI3K)
Omipalsib (PI3K/mTOR)
OSI-027 (mTOR)
AZD6482 (PI3Kb)
GDC0941 (PI3K)
NVP-BEZ235 (PI3K/mTORC1/2)
AZD8055 (mTORC1/2)
Everolimus (mTOR)
Other CDK4
CCND1
Palbociclib (CDK4/6)  
Basal-like 1 Cell cycle POLR1D
POLD4
CDC25A
CDCA7
BIRC3
WEE1
ZM447439 (AURKA/B)
PHA-793887 (CDK2/5/7)
Vinblastine (Microtubules)
MLN8237 ((AURKA)
BI-2536 (PLK1/2/3)
Bortezomib (Proteasome)
DNA repair ATR
HMCES
LIG3
KU-559333 (ATM)
NU7441 (DNAPK)
BMN-673 (PARP1)
Gemcitabine (DNA replication)
Camptothecin (TOP1)
Basal-like 2 DNA repair RAD50 TERF1 Olaparib (PARP)
CP466722 (ATM)
Carboplatin (DNA akyl)
Temozolomide (DNA akyl)
Cyclophosphamide (DNA akyl)
Developmental pathways WNT3
JAG1
NODAL BMPR1A RSPO2
SMAD9
  
MAPK signalling MAP3K1
MAP2K4
Trametinib (MEK1/2)
PD0325901 (MEK1/2)
Refametinib (MEK1/2)
Slumetinib (MEK1/2)
 
Mesenchymal Adhesion/motility RAC1
ITGAV
RSPO1
CD44
ITGB3
SL0101 (RSK) TGFβRI inhibitor (SB-505124)
JNK Inhibitor VIII (JNK)
EHT 1864 (Rac GTPases)
BIRB 0796 (p38/JNK2)
Growth factor FGFR1
FRS2
NGFR
Ponatinib (RTK)
Midostaurin (kinase)
BX796 (kinase)
Axitinib (multi − RTK)
Retinoic acid receptor alpha RARA Tretinoin (RARA agonist)  
Global hypomethylation and increased PRC2 activity
Hypermethylation of immune response and antigen presentation promoter regions
Tazemetostat (EZH2 inhibitor)
CPI-1205 (EZH2 inhibitor)
MAK-683 (EED inhibitor)
Tazemetostat (EZH2 inhibitor)
CPI-1205 (EZH2 inhibitor)
MAK-683 (EED inhibitor)
  1. Data in the table are aggregated from Lehmann et al. [58] and Asghar et al. [74]. Abbreviations: TNBC triple negative breast cancer, PRC2 polycomb repressive complex 2, RTK receptor tyrosine kinase