# New Achievements for the Treatment of Triple-Negative Breast Cancer
## 1 Introduction
Anti-programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) antibodies, androgen receptor blockers, tumor necrosis factor-related apoptosis-inducing ligand receptor agonists and transforming growth factor-\(\beta\) antagonists represent also targeted agents for TNBC [28]. Moreover, signal transducer and activator of transcription 3 (STAT3) [29], EGFR [30], gamma-butyrobetaine hydroxylase (BBOX1) [31], cyclin-dependent kinases CDK12/CDK13 [32], mammalian transcription factor BACHI [33], cMET oncogene [34] and integrin subunit alpha-V gene (ITGAV) [35] have been described as potential therapeutic targets for TNBC in the literature [36]. It is also known that other pathways, such as the insulin-like growth factor-1 (IGF-1)/insulin-like growth factor receptor-type 1 (IGF-1R)--focal adhesion kinase (FAK)--yes-associated protein (YAP) transduction pathway, are able to trigger the growth of TNBC cells [37; 38]. Dysfunctions of micro RNAs (miRNAs), a class of \(\sim\)22 bp noncoding regulatory RNAs, may play an important role in the initiation and progression of cancer, and recent studies on the possible involvement of miR-331-3p [39], miR-490-3p [40], miR-424-5p [41] and miR-335-3p [42] in the tumor microenvironment have been carried out in TNBC. Neoadjuvant chemotherapy (NACT) is an important form of therapy for TNBC patients, though with limited effectiveness, narrow response durations and considerably toxic profiles [43]. Platinum-based NACT has been recently reviewed for the treatment of TNBC [44]. In the last years, great effort has been spent to identify new predictive biomarkers and relative therapies [45; 46]. Moreover, novel drug combinations and nanotechnology may represent promising strategies for the treatment of TNBC [47; 48]. The combination of anti-angiogenic therapy and immunotherapy has been used in the treatment of advanced metaplastic breast carcinoma (MBC) [49]. In recent studies, it has been suggested as an interesting strategy to combat TNBC [50; 51]. It is noteworthy that there are still no FDA-approved targeted therapies for patients with TNBC. The use of an old drug for a new disease indication, named drug repositioning or repurposing, is a very promising strategy used in different fields of drug discovery [52]. Recently, it has also been proposed for targeted therapy in TNBC, as for the anti-leprotic drug clofazimine, which efficiently suppresses tumor growth and is correlated with in vivo inhibition of the Wnt pathway [53]. Adoptive cell therapy, particularly chimeric antigen receptor (CAR)-modified T cell therapy, has gained much attention in the last years [54]. CAR T cell-based immunotherapy redirects the patient's immune system to directly recognize and eradicate tumor cells expressing tumor-associated antigens (TAAs) [55]. However, unlike the remarkable clinical success of CAR-T cell therapies in hematologic cancer, resulting in FDA approval of Kymriah and Yescarta, the development of this type of therapy for solid tumors has been much slower. Recent studies show that the combination of CAR-T cells with other therapies seems to improve the clinical outcome in patients with TNBC [56]. Finally, the Coronavirus disease (COVID-19) pandemic [57] induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 completely reprioritized healthcare resources [58; 59]. The neglect of breast cancer (particularly TNBC) patients during the outbreak could have negatively impacted their overall survival, as delays in treatment and medical consulting are essential for tumor progression and metastasis. Moreover, it should be considered that SARS-CoV-2 is a respiratory virus, with systemic consequences in the management of TNBC patients with metastatic versus localized disease. This review is focused on the novel therapies used for the treatment of TNBC, including nutraceuticals, and studies regarding recent updates obtained in medicinal chemistry in this field.