Paclitaxel's Mechanistic and Clinical Effects on Breast Cancer

Abstract

Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer (BC). Unfortunately, the resistance of BC to PTX treatment is a great obstacle in clinical applications and one of the major causes of death associated with treatment failure. Factors contributing to PTX resistance, such as ABC transporters, microRNAs (miRNAs), or mutations in certain genes, along with side effects of PTX including peripheral neuropathy or hypersensitivity associated with the vehicle used to overcome its poor solubility, are responsible for intensive research concerning the use of PTX in preclinical and clinical studies. Novelties such as albumin-bound PTX (nab-PTX) demonstrate a progressive approach leading to higher efficiency and decreased risk of side effects after drug administration. Moreover, PTX nanoparticles for targeted treatment of BC promise a stable and efficient therapeutic intervention. Here, we summarize current research focused on PTX, its evaluations in preclinical research and application clinical practice as well as the perspective of the drug for future implication in BC therapy.

Keywords: Paclitaxel; anti-cancer therapy; breast cancer; chemotherapy; nanomedicine; phytochemicals.

Figure 1

Mechanism of action of PTX. Anti-tumor mechanism of action of PTX leading to stabilization of microtubule, cell arrest, and subsequent apoptosis (A). PTX also causes activation of the immune response contributing to tumor eradication (B). The ability of PTX to inactivate Bcl-2 via phosphorylation of the anti-apoptotic protein resulting in apoptosis (C). Participation of PTX in the regulation of certain miRNAs associated with the modulation of tumor progression (D). Regulation of calcium signaling by PTX results in PTX-induced release of cyto C from the mitochondria and programmed cell death.

Figure 2

Transcytosis, a receptor-mediated transport of nab-PTX into tumor cells.