Targeting overexpressed surface proteins: A new strategy to manage the recalcitrant triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous cancer that lacks all three molecular markers, Estrogen, Progesterone, and Human Epidermal Growth Factor Receptor 2 (HER2). This unique characteristic of TNBC makes it more resistant to hormonal therapy; hence, chemotherapy and surgery are preferred. Active targeting with nanoparticles is more effective in managing TNBC than a passive approach. The surface of TNBC cells overexpresses several cell-specific proteins, which can be explored for diagnostic and therapeutic purposes. Immunohistochemical analysis has revealed that TNBC cells overexpress α_Vβ₃ integrin, Intercellular Adhesion Molecule 1 (ICAM-1), Glucose Transporter 5 (GLUT5), Transmembrane Glycoprotein Mucin 1 (MUC-1), and Epidermal Growth Factor Receptor (EGFR). These surface proteins can be targeted using ligands, such as aptamers, antibodies, and sugar molecules. Targeting the surface proteins of TNBC with ligands helps harmonize treatment and improve patient compliance. In this review, we discuss the proteins expressed, which are limited to α_Vβ₃ integrin proteins, ICAM-1, GLUT-5, MUC1, and EGFR, on the surface of TNBC, the challenges associated with the preclinical setup of breast cancer for targeted nanoformulations, internalization techniques and their challenges, suggestions to overcome the limitations of successful translation of nanoparticles, and the possibility of ligand-conjugated nanoparticles targeting these surface receptors for a better therapeutic outcome.