The transcriptional factors such as Sox2, Oct4, and Nanog act as master regulators of pluripotency and maintain the undifferentiated state of BC cells.70 Of the basal-like breast carcinomas, 43% exhibit higher Sox2 expression, indicating a less differentiated phenotype.71 Another member of the Sox family, Sox4, induces changes associated with the EMT process that is responsible for increased invasiveness and mobility of cancer cells in vivo.72 Recently, the ability of BCSCs to undergo EMT has been scrutinized, L-ANAP leading to the identification of partial EMT. resistance to cellular insults have come into the limelight. As breast cancer stem cells (BCSCs) are dormant in nature, it is highly likely that they fail to directly respond to the cytotoxic drugs which are meant for ablating rapidly proliferating cells. Furthermore, the absence of well-characterized, drug-able surface markers to date, has limited the application of targeted therapies in complete eradication of the disease. In this review, our intent is to discuss versatile therapeutics in practice followed by discussing the upcoming L-ANAP therapy strategies in the pipeline for BC. Furthermore, we focus on the roles played by BCSCs in mediating the resistance, and therefore, the aspects of new therapeutics against BCSCs under development that may ease the burden in future has also been discussed. expression. BC cells belonging to luminal B subgroup usually show poorer prognosis than luminal A, but respond better to standard chemotherapy. Since patients of this subgroup also show high expression, targeted therapy for might also be employed in some cases.4 In HER2+, BCs, which have amplification or overexpression of the HER2/ERBB2 oncogene, are generally treated with anti-HER2 therapies including the antibody drug trastuzumab and small molecule inhibitor lapatinib. Basal-like BC lacks the hormonal receptors as well as HER2 receptor and therefore is often known as triple negative breast cancer (TNBC). Standard chemotherapeutic regimens involving platinum-based drugs are majorly administered for treating TNBCs. Majority of BC patients (~77%) have hormonal receptor-positive diseases, which comprise 23.7% from ER+/PR+/HER2? (luminal A) and ~53% from ER+/PR+/HER2+ (luminal B). Approximately, 23%C30% of BC patients show HER2 amplification. TNBC represents about 10%C12% of the total BC population.4 Endocrine therapy is currently the gold SPTAN1 standard treatment regimen to treat the hormone receptor+ BCs. This therapy works either by making the hormone effect ineffective or by lowering the hormone level itself. Therapeutic drugs prescribed to the patients include 1) tamoxifen, which acts by blocking the estrogen uptake by ER; 2) exemestane, anastrozole, and letrozole that belong to aromatase inhibitor class of drugs, which inhibits the conversion of androgens to estrogens thereby depleting estrogen in the body; 3) leuprolide and goserelin (luteinizing hormone-releasing hormone analogs), these drugs suppress the synthesis of hormone from the ovary; and 4) fulvestrant (a specific ER inhibitor), which makes it suitable for refractory BC patients. Administration of the above drugs for treating hormone receptor+ BC is recommended until there is clinical resistance or metastasis, where chemotherapy is employed.5 As different endocrine drugs work by distinct mechanism, a combinatorial approach can show improved efficacy. However, the effectiveness of this combination treatment has not been proved well in the patient scenario.5 Therefore, the current consensus is that both endocrine therapy-na?ve advanced BC and high endocrine-sensitive patients can benefit from the combination endocrine therapy.6 The patient group having HER2 gene amplification or protein overexpression is generally administered molecular targeted therapy; a range of targeted drugs have been approved as single agent or in combination with standard chemo regimen. The receptor-targeted therapeutic agents include 1) trastuzumab (specific anti-HER2 monoclonal antibody [mAb]); 2) ado-trastuzumab emtansine, which is trastuzumab conjugated with emtansine (microtubule inhibitor); 3) pertuzumab (specific anti-HER2 mAb with distinct binding site on HER2 extracellular region compared to trastuzumab); L-ANAP 4) lapatinib, a small molecule inhibitor (TKI) capable of inhibiting both HER2 and epidermal growth factor receptor (EGFR) signaling. The standard regimen for early stage HER2+ cases includes neoadjuvant therapy with a combination of HER2 targeted therapy and chemotherapy.7 Subsequently, this treatment is followed by surgery, radiotherapy, and 1 year of HER2-targeted therapy. Endocrine adjuvant can be added based on the specific receptor status in patient. The successful advent of molecular targeted therapy against HER2+ BC can be seen by the substantial increase in overall survival (OS) of patients from ~1.5C5 years.7 TNBC is aggressive by nature and defiant to treat as well when compared to hormone-positive and HER2+ BC. TNBC can be further subdivided into six subtypes based on transcriptomic heterogeneity and response to chemotherapy. These subtypes are mesenchymal (M), a mesenchymal stem-like (MSL), basal-like (BL1 and BL2), a luminal androgen receptor (LAR), and an immunomodulatory (IM) type.8 Both M and MSL subtypes.