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Review
. 2022 Aug 29;15(1):121.
doi: 10.1186/s13045-022-01341-0.

Recent advances in therapeutic strategies for triple-negative breast cancer

Yun Li #  1 , Huajun Zhang #  1 , Yulia Merkher  2 , Lin Chen  1 , Na Liu  3 , Sergey Leonov  4   5 , Yongheng Chen  6   7
Affiliations
Review

Recent advances in therapeutic strategies for triple-negative breast cancer

Yun Li et al. J Hematol Oncol. .

Abstract

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC) with a poor prognosis. Current treatment options are limited to surgery, adjuvant chemotherapy and radiotherapy; however, a proportion of patients have missed the surgical window at the time of diagnosis. TNBC is a highly heterogeneous cancer with specific mutations and aberrant activation of signaling pathways. Hence, targeted therapies, such as those targeting DNA repair pathways, androgen receptor signaling pathways, and kinases, represent promising treatment options against TNBC. In addition, immunotherapy has also been demonstrated to improve overall survival and response in TNBC. In this review, we summarize recent key advances in therapeutic strategies based on molecular subtypes in TNBC.

Keywords: Combination therapy; Immunotherapy; Targeted therapy; Triple-negative breast cancer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Classification and therapeutic options for TNBC. ADC: antibody‒drug conjugates; AR: androgen receptor; LAR: luminal androgen receptor; M: mesenchymal; MSL: mesenchymal-stem-like; PARP: poly-adenosine diphosphate ribose polymerase; PI3K: phosphoinositol-3 kinase; TKI: tyrosine kinase inhibitor; and TNBC: triple-negative breast cancer
Fig. 2
Fig. 2
Potential therapeutic targets and appropriate drugs in TNBC. The schematic shows several major abnormal signaling pathways (green), excessive activated receptors (purple), and other key molecules involved in proliferation and progression (blue) in TNBC. Drugs specifically targeting molecules are indicated by red arrows, and the number represents the following agents: (1) VEGFR inhibitors (cediranib, apatinib, lenvatinib) and VEGFR mAb (bevacizumab); (2) EGFR inhibitors (afatinib, gefitinib), EGFR mAbs (nimotuzumab, panitumumab, cetuximab, and SCT200) and ADCs (anti-EGFR-IL-dox and U3-1402); (3) IGF1R blocking drugs (linsitinib, NVP-AEW541, and BMS-754807); (4) CXCR4 antagonists (balixafortide) and CXCR4-binding peptide (DV1); (5) Src inhibitors (dasatinib and BJ-2302); (6) MEK inhibitors (trametinib and binimetinib); (7) ERK inhibitors (BL-EI001 and nifetepimine); (8) PI3K inhibitors (alpelisib and buparlisib); (9) AKT inhibitors (ipatasertib and capivasertib); (10) mTOR inhibitors (everolimus and MLN0128); (11) CYP17 inhibitors (abiraterone acetate and orteronel); (12) AR inhibitors (bicalutamide, enzalutamide, and enobosarm); (13) microtubule stabilizer (taxanes, vincristine, and eribulin); multiple target inhibitors (AMXI-5001 and ixabepilone); and ADCs (mirvetuximab, soravtansine, CX-2009, and SAR566658); (14) endocrinotherapy (tamoxifen and letrozole); (15) HDAC inhibitors (panobinostat, belinostat, chidamide, romidepsin, entinostat, and CUDC-907); (16) PARPi (olaparib, veliparib, talazoparib, niraparib, and rucaparib) and platinum-based agents (cisplatin and carboplatin); (17) CDK inhibitors (trilaciclib, palbociclib, abemaciclib, ribociclib, dinaciclib, and PF-06873600); and (18) p53 agonist (PRMIA-1 and APR-246). ADCs, antibody‒drug conjugates; AR: androgen receptor; AXL: AXL receptor tyrosine kinase; BRCA: breast cancer susceptibility gene; BRD4: bromodomain containing 4; CDK: cyclin-dependent kinases; CXCR4: C-X-C chemokine receptor type 4; CYP17: 17-[α]-hydroxylase/17:20-lyase (CYP17); ER: estrogen receptor; DHT: dihydrotestosterone; EGFR: epidermal growth factor receptor; FGFR: fibroblast growth factor receptor; HDAC: histone deacetylase; IGF1R: type 1 insulin-like growth factor receptor; PARP: poly-adenosine diphosphate ribose polymerase; and VEGFR: vascular endothelial growth factor receptor
Fig. 3
Fig. 3
Summary of current combinations for TNBC treatment in clinical trials. The therapeutic strategies include immunotherapy and various molecular targeted therapies, including intracellular pathway inhibitors, cell cycle inhibitors, and AR inhibitors. ADCs: antibody‒drug conjugates; BRD4: bromodomain containing 4; ICB: immune checkpoint blockade; mAb: monoclonal antibody; and PARP: poly-adenosine diphosphate ribose polymerase
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