An Overview of Emerging Trends in Targeted Therapy of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a biologically diverse, highly aggressive class of breast cancer defined by the absence of estrogen, progesterone, and HER2 receptors. It accounts for approximately 10%-20% of all invasive breast cancers, and disproportionately affects women of younger ages and from minority groups. TNBC is distinguished by delayed diagnosis requiring special techniques, rapid metastatic progression, and limited treatment options compared with other breast cancers. Chemotherapy remains the mainstay but patients face higher relapse rates and overall survival is significantly reduced. TNBC represents a diverse array of subtypes, whose molecular differences impact their pathological behavior and response to therapy. Newer molecular markers in various stages of clinical and preclinical development show promise towards improving the management of TNBC patients. Membrane receptor proteins like trop2, nectin-4, LIV-1, gpNMB, CXCR4, DDR1, and PD-L1 have been targeted with antibody-drug complexes. Synthetic small molecules and antisense oligonucleotides have been employed for inhibition of internal cellular components like PARP enzyme and expression of genes related to cancer progression. The molecular makeup of the tumor microenvironment is also a significant factor in addressing TNBC metastasis. In conclusion, the stratification of TNBC patients on their molecular subtype needs to be more widely adopted, and a calculated combination of current and emerging strategies is needed to effectively address TNBC in the clinic.