Novel strategies to prevent the development of multidrug resistance (MDR) in cancer

// Jinglu Wang 1, 2 , Nicole Seebacher 2 , Huirong Shi 1 , Quancheng Kan 1 and Zhenfeng Duan 1, 2 1 Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of China 2 Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA Correspondence to: Quancheng Kan, email: qckan19632012@163.com Zhenfeng Duan, email: zduan@mgh.harvard.edu Keywords: drug resistance, MDR, prevention, Pgp, Pgp inhibitor Received: April 21, 2017      Accepted: June 26, 2017      Published: July 12, 2017 ABSTRACT The development of multidrug resistance (MDR) is one of the major challenges to the success of traditional chemotherapy treatment in cancer patients. Most studies to date have focused on strategies to reverse MDR following its development. However, agents utilizing this approach have proven to be of limited clinical use, failing to demonstrate an improvement in therapeutic efficacy with almost no significant survival benefits observed in cancer clinical trials. An alternative approach that has been applied is to prevent or delay MDR prior or early in its development. Recent investigations have shown that preventing the emergence of MDR at the onset of chemotherapy treatment, rather than reversing MDR once it has developed, may assist in overcoming drug resistance. In this review, we focus on a number of novel strategies used by small-molecule inhibitors to prevent the development of MDR. These agents hold great promise for prolonging the efficacy of chemotherapy treatment and improving the clinical outcomes of patients with cancers that are susceptible to MDR development.