A potential target for anti-cancer drugs is the actin cytoskeleton; however, it has been unattainable because the toxicity associated with disabling this target has been unacceptable. The actin cytoskeleton is a desirable target because it controls many fundamental processes in the cancer cell such as cell growth, migration and interaction with the surrounding environment. We have identified a way to attack specific actin filament populations within cells by using drugs that target specific isoforms of the actin-associated protein tropomyosin.
Actin/Tpm3.1 filaments are the major actin cytoskeleton structures in all types of cancer cells. We have demonstrated that compounds that target the cancer tropomyosin Tpm3.1 synergise with microtubule-targeting drugs to reduce tumour growth (Mol Cancer Ther, 2017; Mol Cancer Res, 2020). This approach also has the potential to selectively disable specific actin filament populations involved in a range of cellular functions.
Pancreatic cancer remains one of the great challenges of medicine. New treatment strategies are urgently required. We use Tissue Micro Arrays (TMAs) to identify candidate therapy targets. In collaboration with the Pancreatic Cancer Group at UNSW we have identified multiple tropomyosin targets (Tpms 3.1, 1.6, 1.8) that regulate different properties of pancreatic tumours. We are testing the ability of different anti-tropomyosin drugs to both improve drug access to the tumour and to kill the tumour cells.