Laboratory-Based Research: My laboratory is focussed on understanding aspects of the biology of solid tumours, and on improving the outcome of treatment of such tumours with chemotherapy.

A major limitation to the use of chemotherapy for solid tumours is poor penetration of drugs through tissue. We have established multilayered cell cultures to study drug penetration in tissue culture. We are using quantitative immunohistochemistry to evaluate the relationship between drug concentration (for fluorescent drugs) or drug effects (using fluorescent antibodies to markers of drug activity) with blood vessels and regions of hypoxia in sections of solid tumours. For many drugs in clinical use, tissue penetration is limited to perivascular regions so that many viable cells are not exposed to lethal concentrations of drug. We are evaluating methods to overcome drug resistance due to limited distribution, including modification of the extracellular matrix, inhibition of the sequestration of basic drugs in acidic endosomes, and co-administration of agents that are activated in hypoxic regions of tumours. We propose a continuum of research from tissue culture models through animal experiments to clinical trials.

A second mechanism whereby solid tumours may be resistant to the effects of anti-cancer drugs is the repopulation of tumour cells between cycles of chemotherapy. Our data suggest that this process can accelerate with time leading to acquired resistance after initial response to treatment. We are studying methods to inhibit selectively this process in tumours by administering cytostatic biological agents between courses of chemotherapy, again with the view of applying this in subsequent clinical trials.

Clinically-Based Research: I have a long-standing interest in improving methods for undertaking clinical trials, and especially in use of endpoints such as quality-of-life that reflect patient benefit directly. We have applied these endpoints in clinical trials for patients with prostate and breast cancer, and are interested in the mechanisms by which chemotherapy may cause fatigue and cognitive dysfunction.

Current and recent research trainees and assistants:


Administrative Assistant:

• Mirella (Mel) Giovinazzo

Laboratory-Based Research:

• Carol Lee (Senior Technician)


• Andrea Fung (PhD student)


• Krupa Patel (PhD student)


• Jas Saggar (PhD student)


• Vithika Sivabalasundaram [Medical student (part-time), 2008-2010]


• Susie Tan (PhD student)


• Dr. Piotr Wysocki (Clinical Research Fellow, 2010)

Clinical Research:

• Laurie Adams (Clinical Trial Nurse)
  
• Dr. Eitan Amir (Clinical Research Fellow, 2009-2011)


• Soo Chin (Clinical Trial Nurse)


• Dr. Alberto Ocana Fernandez (Clinical Research Fellow, 2008-)


• Dr. Bostjan Seruga (Clinical Research Fellow, 2008-2010)


• Anna Dodd (Clinical Research Assistant)


• Dr. Saroj Niraula (Clinical Research Fellow, 2009-2011)

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