Title:Resistance to Intervention: Paclitaxel in Breast Cancer
Volume: 21
Issue: 10
Author(s): Vipin Mohan Dan, Reji Saradha Raveendran and Sabulal Baby*
Affiliation:
- Phytochemistry and Phytopharmacology Division, Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Pacha-Palode 695562, Thiruvananthapuram, Kerala,India
Keywords:
Paclitaxel, breast cancer, resistance, signal pathways, combination therapy.
Abstract: Breast cancer stands as the most prevalent cancer in women globally, and contributes to the
highest percentage of mortality due to cancer-related deaths in women. Paclitaxel (PTX) is heavily
relied on as a frontline chemotherapy drug in breast cancer treatment, especially in advanced metastatic
cancer. Generation of resistance to PTX often derails clinical management and adversely affects
patient outcomes. Understanding the molecular mechanism of PTX resistance is necessary to device
methods to aid in overcoming the resistance. Recent studies exploring the mechanism of development
of PTX resistance have led to unveiling of a range novel therapeutic targets. PTX resistance pathways
that involve major regulatory proteins/RNAs like RNF8/Twist/ROR1, TLR, ErbB3/ErbB2, BRCA1-
IRIS, MENA, LIN9, MiRNA, FoxM1 and IRAK1 have expanded the complexity of resistance mechanisms,
and brought newer insights into the development of drug targets. These resistance-related targets
can be dealt with synthetic/natural therapeutics in combination with PTX. The present review
encompasses the recent understanding of PTX resistance mechanisms in breast cancer and possible
therapeutic combinations to overcome resistance.