Establishment and characterization of cancer cell populations and clones resistant to the anticancer drug candidate M2

Abstract

Drug resistance is one of the greatest impediments in the treatment of cancer that adds a layer of challenge in anticancer drug development. A number of chemotherapeutic drugs, such as Cisplatin and doxorubicin, already exist and are widely used in the market, but not without the same challenge of resistance. Here, we iterate a spectrum of intracellular mechanisms cells often yield to gain resistance to different types of anticancer drugs, with the Primary focus on the establishment and characterization of M2-resistance cancer cell populations and clones. M2 is an anticancer drug candidate currently under development with a target-based mechanism. Previous studies in our lab strongly suggest that M2 inhibits cellular proliferation by interrupting the assembly of Minichromosome maintenance protein complex (MCM) complexes at the origin of replication, which plays a vital role in both the initiation and elongation process of DNA replication. The aim of this study is to establish M2-resistant cells over a period of time and analyse different traits found in them, with hopes to further our knowledge on M2. Our data show a correlation between chromatin-bound MCM level and S-phase progression speed, which was consistently observed among the resistant population ‘R8’ and different clones. The results from our study are in line with the known working mechanism of M2, and also hint at the importance of the established resistant cells for future studies such as in investigating methods to overcome resistance to M2.

Date of Award	2019
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology