utspeaks: a medicated nation (part 2: assoc prof mary bebawy)
DESCRIPTION
UTSpeaks: A medicated nationHas Australia lost its way in a pharmaceutical love affair?Professor Charlie Benrimoj and Associate Professor Mary Bebawy from the University of Technology, Sydney present at this public lecture on prescription medication held on 13 September, 2011.How many pills will you take today? Do you really need them? What good (and bad) will they do you?For many of us prescription medications mean the difference between good and ill-health. There’s no denying their important place in fostering well-being for many. But is it time to reflect on the complex forces at work when managing disease and medications and how this impacts you the consumer?Featuring leading UTS researchers in pharmacy and using example case studies, this public lecture takes a critical look at how medications are prescribed and consumed in Australia. It considers whether we are getting value for money, the ideal health outcomes we hope for and whether new approaches to the responsible use and explanation of medications could be adopted.Speakers:Professor Shalom (Charlie) BenrimojCharlie Benrimoj is head of the newly-created UTS School of Pharmacy. Formerly he was Foundation Professor of Pharmacy Practice then Dean of the Faculty of Pharmacy and then Pro-Vice Chancellor (Strategic Planning) at the University of Sydney. He is a visiting professor at the University of Granada with research interests in the future of community pharmacy. He is widely published - co-authoring Community Pharmacy: Strategic Change Management in 2007. He was Australian Pharmacist of the Year in 2000 and received the Andre Bedat award in 2010 from the International Pharmacy Federation.Associate Professor Mary BebawyMary Bebawy has spent more than 14 years in research and teaching positions in academia and two years in industry as a post doctoral preclinical drug development scientist with Johnson and Johnson, Research. She has consulted to academia and industry on assay development, drug discovery and cancer resistance mechanisms. At the UTS School of Pharmacy she specialises in the role and regulation of the xenobiotic cascade in drug disposition and in cancer multidrug resistance (MDR).UTSPEAKS: is a free public lecture series presented by UTS experts discussing a range of important issues confronting contemporary Australia.Use the hashtag #utspeaks to tweet about the lecture on Twitter.TRANSCRIPT
Resistance in cancer therapy
M.BEBAWY – A MEDICATED NATION – 13 SEPT 2011
Evidence Based
Approach based on extensive research and clinical precedent.
• Treatment goal - curative, prolong life, palliative• Tumor characteristics - cytokinetics, size, location,
markers (Her2+, EGFR+, KRAS). • Stage - local, regional, systemic• Mechanism of drug action - phase vs non-phase specific• Tumor responsiveness – reoccurrence?• Dose limiting toxicity - life time maximal dose
Cancer – Proliferation, Invasion & Metastasis
Schmidt CC. Magazine 2 (1), 2007
Resistance
Gong J, Jaiswal R, et al. Cancer Treatment Reviews 2011 (in press)
Increased drug efflux
Altered molecular
targets
Vesicular sequestration
Increased drug metabolism
Decreased drug influx
Increased DNA repair
Altered cellular death apparatus
Altered cell cycle checkpoints
Multiple Drug Resistance (MDR)
Unique Resistance – cross resistance
Cause of treatment failure in 90% patients with metastatic disease
Functionally redundant
Poor prognosis and outcome
Unique Resistance – cross resistance
Cause of treatment failure in 90% patients with metastatic disease
Functionally redundant
Poor prognosis and outcome
DRUG EFFLUX
Fu, et al. Int. J. Cancer 109, 174-181, 2004
MDR ACQUISITION
DRUG INDUCED MDR
Kota BP, et al. Pharmacological Research 62 (2010) 426–431
CELL COMMUNICATION
• 0.1-1 µm vesicles
• Released from all cell types
• Image of donor cell (membrane, cytoplasmic, nuclear constituents)
• Transfer bioactive molecules between cells
• Biomarkers: thrombosis and inflammation
• 0.1-1 µm vesicles
• Released from all cell types
• Image of donor cell (membrane, cytoplasmic, nuclear constituents)
• Transfer bioactive molecules between cells
• Biomarkers: thrombosis and inflammation
Pro-coagulant
Disease
Pro-inflammatory
Microparticles: Bind to Cancer Cells
CEM
+ VLBMP
MICROPARTICLES: Alternative Cancer MDR PathwayBebawy M et al., Leukemia (2009) 23, 1643–1649
MPs shed
MPs transfer nucleic acids to sensitive cells to reduce drug uptake
IMPLICATIONS
