Paclitaxel resistance in breast cancer: Current challenges and recent advanced therapeutic strategies

Breast cancer (BC) is one of the leading causes of cancer-related deaths among women worldwide. Paclitaxel (PTX), a chemotherapeutic agent derived from the taxane family, is commonly used in treating BC due to its ability to disrupt microtubule dynamics and induce cell death. However, resistance to PTX presents a significant challenge, as it diminishes the drug's effectiveness and can lead to treatment failure. This review explores the mechanisms by which PTX exerts its effects and the various factors contributing to resistance. These factors include genetic mutations that affect tubulin dynamics, the role of non-coding RNAs, molecular pathways involved in chemoresistance, epigenetic changes, post-transcriptional modifications, increased activity of ABC transporters that promote drug efflux, immunosuppressive interactions within the tumor microenvironment, and resistance mediated by autophagy. This review also explores strategies to overcome PTX resistance, including molecular and genetic innovations, combination therapies, and nanotechnology-based approaches. These strategies may improve PTX efficacy and enhance treatment outcomes for BC patients.