Recent strategies to overcome breast cancer resistance

Abstract

Breast cancer is potentially a lethal disease and a leading cause of death in women. Chemotherapy and radiotherapy are the most frequently used treatment options. Drug resistance in advanced breast cancer limits the therapeutic output of treatment. The leading cause of resistance in breast cancer is endocrine and hormonal imbalance, particularly in triple negative and HER2 positive breast cancers. The efflux of drugs due to p-gp's activity is another leading cause of resistance. Breast cancer resistant protein also contributes significantly. Strategies used to combat resistance include the use of nanoparticles to target drug delivery by co-delivery of chemotherapeutic drugs and genes (siRNA and miRNA) that help to down-regulate genes causing resistance. The siRNA is specific and effectively silences p-gp and other proteins causing resistance. The use of chemosensitizers is also effective in overcoming resistance. Chemo-sensitizers sensitize cancer cells to the effects of chemotherapeutic drugs. Novel anti-neoplastic agents such as antibody-drug conjugates and mesenchymal stem cells are also effective tools used to improve the therapeutic response in breast cancer. Similarly, combination of photo/thermal ablation with chemotherapy can act to overcome breast cancer resistance. In this review, we focus on the mechanism of breast cancer resistance and the nanoparticle-based strategies used to combat resistance in breast cancer.

Keywords: Breast cancer; Chemo-sensitizers; Co-delivery of drug and genes; Drug resistance; Novel anti-neoplastic agents.