Building an anti-cancer therapy out of the basic science of the actin cytoskeleton

Professor Peter Gunning
Head of School
School of Medical Sciences
UNSW Medicine

Abstract: The actin cytoskeleton participates in virtually every cytoplasmic function in mammalian cells. This is achieved by building not just one type of actin filament but rather, distinct types of filaments with different functional characteristics which have become optimised for different physiological roles. Variation in the composition of actin filaments is largely provided by the family of tropomyosins which co-polymerise with actin. Tropomyosin isoforms regulate filament interactions with binding proteins and motor proteins. Discovery of the mechanism of action of tropomyosins and the reliance of cancer cells on a specific isoform of tropomyosin opened the door to the development of anti-cancer drugs which target this tropomyosin. Anti-tropomyosin drugs show up to 20-fold synergy with anti-microtubule drugs currently used in the clinic. This synergy provides a clear path to the clinic for anti-tropomyosin drugs but has also provided a novel approach to understanding the functional collaboration of the actin cytoskeleton with microtubules. 

Bio: Peter did his BSc(Hons) and PhD at Monash University in nerve regeneration and then moved to Stanford University. His first postdoc was with Eric Shooter on nerve growth factor regulation of neurogenesis and his second postdoc with Larry Kedes involved cloning the genes encoding human contractile apparatus. Upon moving back to Australia first at the CMRI, then at the Children’s Hospital at Westmead and finally at UNSW his lab has focussed on the role of actin and tropomyosin isoforms in regulating the function of the actin cytoskeleton. Peter has been a member of the Board of the NSW Cancer Council and subsequently the Board of the Cancer Institute NSW and Chair of their Cancer Research Advisory Committees. He was the inaugural Chair of the Division of Research at the Children’s Hospital at Westmead and subsequently the Deputy Dean (Research) and then Head of the School of Medical Sciences in the Faculty of Medicine at UNSW.