Treatment Strategies Against Triple-Negative Breast Cancer: An Updated Review

Figures & data

Figure 1 Summarized conventional and novel targeted approach to treat triple-negative breast cancer.

Abbreviations: AR, androgen receptor; PARP, poly (ADP-ribose) polymerase; PD-L1, Programmed death ligand 1; PI3K/AKT/mTOR, Phosphatidylinositol-3-kinase (PI3K)/AKT and the mammalian target of rapamycin (mTOR).

Table 1 Therapeutic Strategies and Targeted Agents That May Be Used in Specific Subtypes of Triple Negative Breast Cancer

TNBC Subtype	Therapeutic Strategies	Therapeutic Targeted Drugs
LAR (luminal androgen receptor)	Inhibit FOXA1, AR signaling, and ERBB4 signaling	PI3K inhibitors Eg, Idelalisib mTOR inhibitors Eg, RapaLink-1, rapamycin, everolimus, Nonsteroidal antiandrogens Eg, bicalutamide
MSL (mesenchymal stem-like)	Inhibit, PI3K, mTOR, EMT, Wnt, TGFβ, MAPK, Rac, Scr, PDGF	Scr inhibitors Eg, Dasatinib, Bosutinib MAPK inhibitors Eg, Dabrafenib, Trametinib PI3K inhibitors Eg, Idelalisib mTOR inhibitors Eg, RapaLink-1, rapamycin, everolimus Growth Factor inhibitors Eg, Vandetanib, Bevacizumab, Pertuzumab, Ramucirumab, Trastuzumab, Axitinib, Cabozantinib, Ceritinib, Erlotinib, Gefitinib, Afatinib, Osimertinib, Olmutinib, Nazartinib, Avitinib, lapatinib, Cetuximab, Panitumumab, Crizotinib, Lenvatinib, Nilotinib, Pazopanib, Regorafenib, Sorafenib, Sunitinib
M (mesenchymal)	Inhibit Scr, TGFβ, EMT, Wnt, PI3K, mTOR, IGF1R, Notch	PI3K inhibitors Eg, Idelalisib Scr inhibitors Eg, Bosutinib, Dasatinib mTOR inhibitors Eg, Rapamycin, Everolimus, RapaLink-1 Growth Factor inhibitors Eg, Erlotinib, Gefitinib, Afatinib, Osimertinib, Olmutinib, Nazartinib, Avitinib, lapatinib, Cetuximab, Panitumumab, Vandetanib, Bevacizumab, Pertuzumab, Ramucirumab, Trastuzumab, Axitinib, Cabozantinib, Ceritinib, Crizotinib, Lenvatinib, Nilotinib, Pazopanib, Regorafenib, Sorafenib, Sunitinib
IM (immunomodulatory)	Inhibit immune signaling	Immune checkpoint inhibitors Eg, Ipilimumab, Nivolumab PARP inhibitors Eg, Olaparib, Rucaparib, Talazoparib and Niraparib) Cytostatics E.g.Cisplatin, Carboplatin, Nedaplatin, Eptaplatin, Oxaliplatin, Lobaplatin, Satraplatin, Mercaptopurine
BL1 (basal-like 1)	Inhibit cell proliferation and DNA damage response	DNA Synthetic inhibitors Eg, Camptothecin, Doxorubicin, Daunorubicin, Topotecan, Irinotecan, Mitomycin PARP inhibitors Eg, Talazoparib, Niraparib, Olaparib, Rucaparib, Cytostatics Eg, Oxaliplatin, Lobaplatin, Satraplatin, Cisplatin, Carboplatin, Nedaplatin, Eptaplatin, Mercaptopurine Mitosis inhibitors Eg, Ixabepilone, Nab-Paclitaxel, Vinorelbine Paclitaxel, Docetaxel,
BL2 (basal-like 2)	Inhibit EGFR, TP63, and MET signaling	mTOR inhibitors Eg, RapaLink-1, everolimus, rapamycin, PARP inhibitors Eg, Talazoparib, Rucaparib, Olaparib, and Niraparib Cytostatics Eg, Oxaliplatin, Cisplatin, Nedaplatin, Carboplatin, Lobaplatin, Satraplatin, Mercaptopurine, Eptaplatin, Growth Factor inhibitors Eg Osimertinib, Gefitinib, Erlotinib, Bevacizumab,Afatinib, Olmutinib, Nazartinib, Vandetanib, Avitinib, lapatinib, Ramucirumab, Cetuximab, Panitumumab, Lenvatinib, Trastuzumab, Nilotinib, Pazopanib, Regorafenib, Sorafenib, Sunitinib Pertuzumab, Axitinib, Cabozantinib, Ceritinib, Crizotinib.

Note: Data from these studies^42–44.

Abbreviations: PI3K, Phosphoinositide 3-kinases; FOXA1, Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A); AR, Androgen receptor; ERBB4, Receptor protein-tyrosine kinase ErbB-4; mTOR, mammalian target of rapamycin; EMT, epithelial–mesenchymal transition; Wnt, Wingless-related integration site; TGFβ, Transforming growth factor beta; MAPK, mitogen-activated protein kinase; Rac, Ras-related C3 botulinum toxin substrate; PDGF, platelet-derived growth factor; IGF1R, insulin-like growth factor 1; PARP, poly adenosine diphosphate-ribose polymerase.

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