Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Table 2 Clinical studies targeting the TNBC cell surface

Gene, Protein	Protein type and function1	Expression in TNBC2	Normal tissue expression	Targeted Drug3	Clinical trials	Ref.
EGFR, Epidermal growth factor receptor	(1) SPT1MP, tyrosine kinase receptor; (2) EGF ligands; (3) RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCγ-PKC and STAT pathways	(1) Protein, n = 316, 37%. (2) Protein, n = 930, 54%. (3) Protein, n = 17, 89%	4High: Placenta. Low: Bladder, liver, skeletal muscle, skin, testis, tonsil, vagina	Ib: Afatinib, Gefitinib, Lapatinib. Ab: Cetuximab, MM 151 Ab mixture	Phase 2	[64-71]
VGFR1-3, Vascular endothelial growth factor receptors 1-3	(1) SPT1MP, tyrosine kinase receptors; (2) VEGF A,B,C,D,PGF ligands; (3) Angiogenesis, lymphangiogenesis, cell survival, migration, chemotaxis, invasion, vascular development and permeability	(1) Genomic, increased copy n = 87, 62%; (2) Genomic, increased copy, n = 35, 29%	6VEGF1: 220 organs- lung, placenta, liver, kidney, heart, brain. VEGF2: 208 organs, lung, cornea, broadly expressed. VEGF3: 121 organs– liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, kidney	Ib: Cediranib, Apatinib, Lucitanib	Phase 2	[72-74]
FGFR1, Fibroblast growth factor receptor 1	(1) SPT1MP, tyrosine kinase receptor; (2) FGF ligands; (3) Proliferation, migration	Genomic, increased copy, n = 76, 9%; mRNA, n = 56, 4%	4High: Gallbladder, esophagus, fallopian tube, placenta. Medium and Low: Broadly expressed	Ib: Lucitanib	Phase 2	[75-78]
GPNMB, Transmembrane glycoprotein NMB	(1) SPT1MP; (2) Possible melanogenic enzyme	mRNA, n = 103, 29%	5High: Skin. Medium: Cervix, uterine, gallbladder. Low: Broadly expressed	ADC: Glembatumumab vedotin (CDX-011)	Phase 2	[79]
TACSTD2, Tumor-asscociated calcium signal transducer 2 (Trop-2 receptor)	(1) SPT1MP; (2) Possible growth factor receptor	Protein, n = 96, 75%	4Medium: Nasopharynx, bronchus, oral mucosa, esophagus, bladder, seminal vesicle, cervix, uterine, skin. Low: Multiple sites	ADC: Sacituzumab govitecan (IMMU-132)	Phase 2	[21]
SLC39A6, Zinc transporter ZIP6 (LIV-1)	(1) MPMP; (2) Possible zinc-influx transporter	Protein, n = 20, 65%	4High: Adrenal gland, endometrium. Medium and low: Broadly expressed	ADC: SGN–Ab and human Ab-MMAE	Phase 1/2	[22,24]
CD274, Programmed cell death 1 ligand 1 (PD-L1)	(1) SPT1MP; (2) Immune tolerance, antitumor immunity	Protein, n = 127, 30.7%	4High: Lung, placenta. Medium: Lymph node, tonsil, spleen. Low: Appendix, colon	Ab: Avelumab, Atezolizumab, BMS-936559, Durvalumab, HLX20, LDP, LY3300054. CAR-T. CSR-T	Phase 1, 2, 3	[80-85]

¹MPMP: Multi-pass membrane protein; SPMP: Single-pass membrane protein; SPT1MP: Single-pass type I membrane protein.

²mRNA: Microarray, protein, immunohistochemistry; n: Number of patient specimens.

³Ib: Small molecule inhibitor; Ab: Inhibitory monoclonal antibody; ADC: Antibody-drug conjugate; hAb: Humanized antibody; CAR-T: CAR-T cells; CSR-T: Chimeric switch receptor modified T cells.

⁴Human Protein Atlas: Protein expression.

⁵Human Protein Atlas: mRNA expression.

⁶UniProt: mRNA expression.