Cancer Drug Resistance

Group Head: Dr John Allen

The Cancer Drug Resistance Group works to improve the scientific basis of chemotherapy by understanding the cellular and molecular processes underlying drug resistance and related problems of drug toxicity and variable drug pharmacokinetics. We aim to identify new mechanisms of anti-cancer drug resistance, to evaluate their clinical significance, and to find ways of overcoming them or at least predicting them in advance. We focus on resistance to new and promising anti-cancer drugs that are being applied to treating common, recalcitrant tumours, including melanoma and multiple myeloma.

Research focus

Drug resistance in melanoma
Australia holds the dubious honour of having the highest melanoma incidence rate in the world. Melanoma is one of the cancers most resistant to chemotherapy. Unless caught early, melanoma is almost invariably fatal.

We are investigating the reticence of melanoma cells to undergo apoptosis (an orderly form of suicide) when damaged by anti-cancer drugs and we hope to understand how important this is in relation to other forms of drug resistance that operate in melanoma cells.

Analysis of resistance to apoptosis is technically challenging as propagation of melanoma cells in vitro alters their properties. Hence, the focus is on genetically manipulated mouse models of human melanoma, where melanomas develop and can be treated in their natural sites of origin, in the presence of a normal immune system.

Drug resistance in multiple myeloma
Multiple myeloma is an incurable cancer of the blood plasma cells that secrete antibodies to fight infection.

The production of antibodies is known to depend on the Unfolded Protein Response (UPR), a system that ensures correct folding and assembly of proteins and the disposal of incorrectly folded or damaged ones - a form of quality control that every complex manufacturing system requires, and cells are no exception.

We believe that dependence on this system is what makes myelomas resistant to many drugs but, conversely susceptible to a new class of new drugs, the proteasome inhibitors. Initial results indicate that markers of the UPR can predict the sensitivity of myelomas to the proteasome inhibitor Velcade both in vitro and in myeloma patients.