Research Projects

Multidrug resistance (MDR) is a major cause of rising global cancer mortality index, and identifying the factors responsible for MDR is crucial to solving MDR-induced cancer recurrences. Copper (Cu) transporters play a significant role in MDR, with two proteins identified in mammalian cells: copper transporter 1 and 2 (CTR1 and CTR2). CTR1 is the high-affinity transporter in the plasma membrane, which forms pores for uptake of Cu and other metal-based drugs upon trimerisation. CTR2 has relatively lower affinity and is mostly associated with internal vesicular structures, possibly aiding in Cu mobilisation. The role of CTR1-CTR2 interaction on drug uptake, intracellular drug accumulation, and MDR development represents an interesting research avenue. CTR2 mediated biogenesis of cleaved CTR1 leads to loss of the cisplatin-binding ectodomain, but no direct evidence has been noted. This study aims to explore if CTR1-CTR2 can regulate drug resistance, focusing on key questions such as whether CTR1 and/or CTR2 are responsible for MDR, what membrane mechanism CTR1-CTR2 adopts for drug uptake, the intracellular fate of CTR1/CTR2-internalized drugs, and what happens to CTR1-CTR2 when cells become drug-resistant. Understanding the molecular basis of drug resistance can enable improved therapeutic modalities and progress towards a cancer-free world.