Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy

Abstract

Paclitaxel (PTX) is a chemotherapeutical agent commonly used to treat several kinds of cancer. PTX is known as a microtubule-targeting agent with a primary molecular mechanism that disrupts the dynamics of microtubules and induces mitotic arrest and cell death. Simultaneously, other mechanisms have been evaluated in many studies. Since the anticancer activity of PTX was discovered, it has been used to treat many cancer patients and has become one of the most extensively used anticancer drugs. Regrettably, the resistance of cancer to PTX is considered an extensive obstacle in clinical applications and is one of the major causes of death correlated with treatment failure. Therefore, the combination of PTX with other drugs could lead to efficient therapeutic strategies. Here, we summarize the mechanisms of PTX, and the current studies focusing on PTX and review promising combinations.

Miniaturized and multiplexed high-content screening of drug and immune sensitivity in a multichambered microwell chip

“…Its primary mechanism of action is to prevent microtubule depolymerization with consequent cell-cycle arrest and death. A secondary mechanism of action is apoptosis due to metabolic stress and mitochondrial damage ( Gallego-Jara et al., 2020 ; Nawara et al., 2021 ).…”

The Influence of Domain Permutations of an Albumin-Binding Domain-Fused HER2-Targeting Affibody-Based Drug Conjugate on Tumor Cell Proliferation and Therapy Efficacy

“…The data presented in this study clearly demonstrate that for HER2-positive cells, additional stimulation of cell proliferation does not improve the therapeutic effect in vivo. In future studies, it would be interesting to investigate how the drug conjugates affect more slowly diving cells, such as cancer stem cells, which are notoriously difficult to eliminate with microtubule-disrupting agents [39].…”

CK1 Is a Druggable Regulator of Microtubule Dynamics and Microtubule-Associated Processes

“…Common side effects also include nausea, vomiting, and diarrhea [ 130 ]. Approaches to limit adverse events but also to overcome resistance, therefore, include combination therapy, e.g., paclitaxel and gemcitabine for the treatment of advanced pancreatic cancer [ 131 ] and numerous other combinations being currently under clinical investigation (reviewed by Nawara et al, [ 132 ]), as well as introducing novel antibody drug conjugates such as ado-trastuzumab emtansine (the maytansine derivative emtansine was conjugated to trastuzumab), which has recently been evaluated and approved for anticancer therapy [ 133 ]. As an alternative to directly targeting microtubules, an intervention on microtubule dynamics can also be achieved by targeting the mitotic kinome responsible for posttranslational modifications of microtubules or MAPs.…”