Cancer Drug Resistance (肿瘤耐药)

Drug resistance in chemotherapy, radiotherapy, molecular targeted therapy and immunotherapy is one of the main causes of death due to cancer. Gene mutations, non-genetic and epigenetic mechanisms to evade drug actions can promote the occurrence of drug resistance and treatment failure. Simultaneous resistance to multiple drugs with different chemical structures, different mechanisms of action and different targets is known as multidrug resistance (MDR). MDR can be related to a variety of mechanisms, including overexpression of drug efflux pumps(ABC transporter family), decreased drug uptake, mutation/loss of receptors, altered apoptotic pathway, enhanced DNA repair and drug metabolism(glutathione S-transferase, CYP450).

ABC transporters are membrane protein superfamily that can mediate MDR mechanism in many types of cancer. Some members of this superfamily includes MDR-associated protein-1(MRP1/ABCC1), breast cancer resistant proteins(ABCG2/BRCP) and P-glycoprotein(P-gp/ABCB1/MDR1). Among them, P-gp is the most extensively characterized efflux pump of MDR, and plays an important role in many cancers such as breast cancer, human lung cancer, ovarian cancer, and colorectal cancer.

The design of antitumor drugs that are able to evade or reverse MDR is rapidly evolving in the anti-cancer drug discovery field. Nanoparticle-based drug delivery platforms have been widely studied in cancer treatment, and become optimal carriers to reverse the limitations encountered in the use of traditional drug formulations, by influencing/manipulating ABC transporter-associated drug efflux mechanisms.