Overcoming treatment resistance in blood cancers

• Honours

Blood cancers can occur when there is a failure of apoptosis (programmed cell death). The drug venetoclax is a powerful inducer of apoptosis in susceptible cancer cells and has revolutionised the treatment of some leukemias. But resistance to venetoclax does occur, and this may be due to multiple mechanisms. We have discovered that activation of the NF-kappaB pathway is a common feature of blood cancer cells that have developed venetoclax resistance (Thijssen, Blood 2022 140(20):2127). This project will investigate the role of pro-inflammatory cytokines in this process, with the aim of developing new strategies to restore patients’ venetoclax sensitivity. Students will use cell culture, cell death assays, flow cytometry, multiplex cytokine assays and proteomics to determine which factors may be driving venetoclax resistance.

In the Huang Lab, we study how cell death is controlled in mammalian cells and use this knowledge to improve outcomes for patients e.g. the success of venetoclax, the BCL2 inhibitor, for treating patients with some types of blood cancers.

We apply innovative techniques e.g. single-cell sequencing (Thijssen, Blood 2022 140(20):2127) and work closely with our clinical colleagues in the development of drugs that target the pro-survival BCL2 proteins.

Together with the lab of Andrew Roberts, we are a vibrant team of ~12 researchers from diverse backgrounds. Team members have a wide range of skills (clinical, molecular biology, biochemistry, genetic or drug screening, in vivo models, bioinformatics) and work collaboratively to tackle some of the most challenging problems in treating patients with leukemias and lymphomas.