Current advances in biomarkers for targeted therapy in triple-negative breast cancer

Figures & data

Figure 1 Biomarker pathways summarized through a “cellular protein network” that demonstrates potential connectivity.

Notes: BiomarkerBase, a biomarker knowledgebase™ developed by Amplion, was used to find registered biomarkers in completed TNBC trials through clinicaltrials.gov with the exception of HER2 and ER/PR. Current literature about the biomarkers was located using PubMed. The protein map is sectioned into plasma (blood), cell surface, cytoplasm, and nucleus. Biomarkers shown in cylinders represent markers found on the cell surface, rounded-edged boxes and circles represent other proteins or metabolites, and curved boxes represent DNA or RNA. Biomarkers examined more thoroughly throughout the review are filled in with gray. A black line with an arrow represents increase, expression, or activation; a dotted lined connected to an X represents inhibition. Star figures denote action such as tumor suppression and cell proliferation.
Abbreviations: EGF, endothelial growth factor; ER, estrogen receptor; GC, glucocorticoid; GR, glucocorticoid receptor; HER2, human epidermal growth factor receptor 2; HGF, hepatocyte growth factor; HK2, hexokinase 2; IGFBP, insulin-like growth factor binding protein; IGF-R1, IGF receptor 1; IL-8, interleukin-8; mTOR, mammalian target of rapamycin; PDK1, phosphoinositide-dependent kinase 1; PIP₂, phosphatidylinositol 4,5-biphosphate; PIP₃, phosphatidylinositol 3,4,5-triphosphate; PKM2, pyruvate kinase M2; pPKM2, phosphorylated version of pyruvate kinase M2; PR, progesterone receptor; SPHK1, sphingosine kinase 1; VEGF, vascular endothelial growth factor; BCRP, breast cancer resistance protein.

Table 1 Potential triple-negative breast cancer biomarkers

Biomarkers	Surrogate biomarker	Prognostic biomarker	Predictive biomarker	PD biomarker
VEGF, VEGFR		3,34	39	3
IL-8	9
EGFR		49,50
pPKM2				17
F1,6BP				17
Lactate/glucose				15,17
IGFBP2		34,60
IGFBP3		55
SPHK1				62,63
c-Kit		10,66,67
c-Met		132
PD-L1			79
STAT1/IRF2BP2	75
S6			79	11
p4E-BP1		91–93		11
SUV39H1				11,95
PTEN	133		60
GPC, PCh		15,101
ALDH1	106	84,104,105
BRCA1 mutations			21
BRCA1 promotor hypermethylation			26,122
GR				124–128
TP53		45,85,122,130

Notes: An overview of the examined surrogate, prognostic, predictive, or PD TNBC biomarkers in addition to current literature found in PubMed that provides support for their potential use.

Abbreviations: EGFR, endothelial growth factor receptor; GPC, glycerophosphocholine; GR, glucocorticoid receptor; IGFBP, insulin-like growth factor binding protein; IL-8, interleukin-8; pPKM2, phosphorylated version of pyruvate kinase M2; SPHK1, sphingosine kinase 1; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.