Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, which is characterized by the absence of estrogen receptor (ER) and progesterone receptor (PR) expression and the absence of human epidermal growth factor receptor 2 (HER2) expression/amplification. Conventional chemotherapy is the mainstay of systemic treatment for TNBC. However, lack of molecular targeted therapies and poor prognosis of TNBC patients have prompted a great effort to discover effective targets for improving the clinical outcomes. For now, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi’s) and immune checkpoint inhibitors have been approved for the treatment of TNBC. Moreover, agents that target signal transduction, angiogenesis, epigenetic modifications, and cell cycle are under active preclinical or clinical investigations. In this review, we highlight the current major developments in targeted therapies of TNBC, with some descriptions about their (dis)advantages and future perspectives.
Highlights
Breast cancer is the type of cancer with the best-characterized molecular classification or subtyping
This study revealed that patients with mutations of other homologous recombination (HR)-related genes might benefit from poly (ADP-ribose) polymerase (PARP) inhibition
Researchers found the HDACi entinostat (ENT) increased the expression of estrogen receptor-a (ERa) and aromatase in breast cancer cells and restored the sensitization of breast cancer cells to the aromatase inhibitor letrozole both in vitro and in vivo. These results suggested that combination of histone deacetylase and aromatase inhibitors could be used to treat ERnegative and endocrine therapy-resistant breast cancer [34]
Summary
Breast cancer is the type of cancer with the best-characterized molecular classification or subtyping. Clinical therapeutic efficacies vary enormously among the different subtypes, with luminal A/B subtypes and triple-negative breast cancer (TNBC) showing the best and worst outcomes, respectively [1]. Due to the aggressive nature and lack of defined molecular targets, the poor overall survival (OS) of metastatic TNBC has remained essentially unchanged over the past two or three decades. Metastatic TNBC has a median OS of approximately 13 months [2], rendering improvement of the clinical outcomes an urgent task in the management of TNBC. Other potential promising targeted therapeutic strategies that are being actively investigated for TNBC include inhibition of signaling kinases (serine/threonine- or tyrosine-type), angiogenesis, epigenetic modifications, and cell cycle.
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