Table 1.
Different chemotherapeutic modalities in clinical practice and novel therapeutic drugs being developed against BC subtypes and their mechanism of action.
| Breast cancer subtype | Drug | Biological target (mechanism of action) |
|---|---|---|
| Hormone positive | In clinical practice | |
| Tamoxifen | Competitively inhibits interaction between ER and estrogen | |
| Fulvestrant | SERD, competitively inhibits estrogen to occupy ER, ER degradation | |
| Aromatase inhibitors (AIs) (exemestane, anastrozole, letrozole) | Blocks conversion of androgens to estrogens | |
| Leuprolide | Reduces production of estrogen and progesterone by the ovary by blocking effects of GnRH on the pituitary gland | |
| Goserelin | Luteinizing hormone-releasing hormone (LHRH) agonist, stops LH production, blocks release of estrogen | |
| Palbociclib (FDA approval: February 2015) | CDK4/6 inhibitors for advanced stage BC along with letrozole | |
| Ribociclib (FDA approval: March 2017) | CDK4/6 inhibitors for advanced stage BC along with letrozole | |
| Abemaciclib or verzenio (FDA approval: October 2021) | CDK4/6 inhibitors for treatment of early-stage BC | |
| Everolimus (FDA approval: July 2012) | mTOR inhibitor, sensitizes hormone-receptor-positive BC to exemestane | |
| In pipeline | ||
| Buparlisib (BKM120) | Pan-class I PI3K inhibitor, combination therapy with fulvestrant, phase III trial (NCT01610284) | |
| Alpelisib | PI3K inhibitor, inhibiting p110 alpha; combination therapy with fulvestrant, phase III trial (NCT02437318) | |
| Taselisib | Alpha-specific PI3K inhibitor; combination therapy with fulvestrant, phase III trial (NCT02340221) | |
| Entinostat | HDAC inhibitor, phase II trial with exemestane (NCT02115282) | |
| Vorinostat | HDAC inhibitor, in combination with tamoxifen, terminated (NCT01194427) | |
| Irosustat | Steroid sulfatase inhibitor with AI, phase II trial completed (NCT01785992) | |
| HER2 enriched | In clinical practice | |
| Trastuzumab | Anti-HER2 mAb interacting with extracellular domain IV of HER2 | |
| Pertuzumab | Anti-HER2 mAb targeting HER2 extracellular domain II, inhibiting HER2 heterodimerization with EGFR, HER3, and HER4 | |
| Lapatinib | Tyrosine kinase inhibitor (TKI) targeting both EGFR and HER2, interacts at ATP-binding site of kinases | |
| Ado-trastuzumab emtansine | Anti-HER2 mAb conjugated with microtubule inhibitor emtansine | |
| Margetuximab (FDA approval: December 2020) | HER2-targeted antibody for metastatic HER2+ BC | |
| Tucatinib (FDA approval: April 2020) | HER2 inhibitor, used in combination with trastuzumab and capecitabine (Xeloda) in metastatic HER2+ BC | |
| In pipeline | ||
| Patritumab | Anti-HER3 mAb in combination with trastuzumab and paclitaxel in phase I/II trial completed (NCT01276041) | |
| Buparlisib with lapatinib and pilaralisib with trastuzumab | Pan class-I PI3K inhibitors, phase I/II trial (NCT01589861), phase I/II trial (NCT01042925) | |
| Lonafarnib | Inhibits Ras activity, combination therapy with trastuzumab and paclitaxel, phase I completed (NCT00068757) | |
| NeuVax + trastuzumab | Immunotherapy for treatment of early-stage HER2+ BC; phase IIb trial (NCT02297698) | |
| Ridaforolimus with trastuzumab | mTOR inhibitors, phase II trial completed (NCT00736970) | |
| Sirolimus with trastuzumab | mTOR inhibitors, phase II trial completed (NCT00411788) | |
| MK-2206 | Allosteric pan-Akt inhibitor; combination therapy with trastuzumab and lapatinib, terminated (NCT00963547) | |
| Triple-negative | In clinical practice | |
| Anthracyclines | Topoisomerase II inhibitors, stabilize DNA breaks and ensuing tumor cell death | |
| Taxanes | Microtubule-stabilizing agent, stabilize GDP-bound tubulin in microtubule, G2/M arrest, cell death | |
| Olaparib | PARP inhibitor, blocks repair of single-strand DNA breaks by base excision repair (BER) system | |
| Talazoparib | PARP inhibitor | |
| Bevacizumab | Antiangiogenic mAb against VEGF bevacizumab + docetaxel anti-VEGF mAb | |
| Atezolizumab (FDA approval: March 2019) | Anti PD-L1 antibody as first-line therapy to locally advanced or metastatic PD-L1-positive TNBC patients | |
| Pembrolizumab (FDA approval: October 2021) | Anti PD-1 antibody for high-risk early-stage TNBC | |
| Trodelvy (sacituzumab) (FDA approval: 2020) | Trop-2 directed antibody and topoisomerase inhibitor drug conjugate for metastatic TNBC patients | |
| In pipeline | ||
| Cetuximab + cisplatin or carboplatin | Anti-EGFR mAb for metastatic TNBC, phase II completed (NCT00463788) | |
| Glembatumumab vedotin | mAb-cytotoxic drug conjugate targeting glycoprotein NMB in TNBC, phase II completed (NCT01997333) | |
| Dasatinib + cetuximab + cisplatin | Src inhibitors, tested in TNBC cell lines | |
The clinical trial number for the drugs in pipeline has been mentioned according to ClinicalTrials.gov.