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Professor Des Richardson, Scholar Rayan Moussa and Dr Zaklina Kovacevic, (pictured at the end of this article) entertained members and guests with an introduction from Des and a presentation from both girls, prior to Kelly Martinez of Australian Rotary Health officially awarding Rayan a plaque as the recipient of the 2011 Rotary Club of Liverpool West & the University of Sydney ARH PhD Scholarship, researching the role of metals for treatment of cancer. An official vote of thanks was then given by District 9690 Governor Elect David Cook, officially Governor come 1 July.
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Australian Rotary Health 2011 Rotary Club of Liverpool West PhD Scholarship Award Presented to Rayan Saleh Moussa (left) by ARH Research Officer Kelly Martinez (right) |
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Official Response from D9690 Governor Elect David Cook on hand for the Presentation with wife Carolyn |
Introduction – Professor Des Richardson
Des leads research into the development of Novel and Selective Anti-Tumour agents at a laboratory at the University of Sydney with more than 30 young scientists.
Anti-Metabolites are a very successful group of anti-tumour agents. The common group are Folate Antagonists, which do experience problems with resistance. Des’ strategy is new and targets iron.
Cancer cells become resistant to conventional therapies and new avenues of investigation are critical with multiple Novel molecular targets.
Iron is an indispensable element (Fe) required for e.g. DNA synthesis, cell cycle progression, respiration, oxygen sensing and energy production.
Fe Chelators are already used to treat Cancer in Clinical Trials. Desferrioxamine (DFO) has been used in a trial with 9 leukaemia patients with some success. Triapine® (Vion Pharmaceuticals) In Phase I/II clinical trials through NCI. Des has tested Dp44mT with much success in nude mice in the reduction of tumours in lung cancer
Investigating the role of iron for treatment of cancer – Rayan Saleh Moussa
The body is made up of trillions of cells, which are constantly dividing to produce more and more cells. This is important for growth and also for repair of damaged cells. The production of new cells is a tightly controlled process with several checkpoints, genes and proteins involved in its regulation.
- In order for a normal cell to transform into a cancer cell, the genes and proteins which regulate its growth must be altered or mutated. The checkpoints are no longer functional, and the cell begins to grow and divide at an abnormal rate, resulting in tumour formation. Mutations can be caused by many environmental and genetic factors, such as radiation and infections.
According to the WHO cancer is a leading cause of death worldwide accounting for 7.6 million deaths in 2008. In Australia alone an estimated 114000 new cases of cancer were diagnosed in 2010
Most common cancer types are prostate, bowel, breast, melanoma and lung cancer.
Some good news is that in the past 2 decades survival rates have increased by more than 30%
Some current treatment options available include surgery, radiotherapy, and chemotherapy and hormone therapy. However, they have many limitations. For example most chemotherapeutic agents are non-selective, and therefore affect normal healthy cells. Other limitations include undesirable side-effects, and the carcinogenic nature of the therapies. So there is a great need for better, more effective treatment options, and that brings me to a class of drugs that our lab has been working on for many years now, known as IRON CHELATORS.
-cancer cells require a lot more iron than normal cells and this is possibly due to their rapid growth. So we find that they have these large storage compartments of iron within them.
-Iron chelators are compounds that bind very tightly to Fe ions; making it biologically inactive meaning it makes iron unavailable for use by the cells
Many studies have demonstrated that fe chelators have inhibitory effects on the growth of tumour cells
And our lab has developed a wide range of Fe chelators and my project aims to try and understand the mechanisms behind this inhibitory effect of Fe chelators on a variety of cancer cells
- Cells are grown and fed in small plastic dishes
- Treated with iron chelators and DNA damaging agents
- DNA and proteins pulled out from the cells 24hrs after treatment and compared to levels in untreated cells (control)
· (each experiment is repeated and this data is then analysed) to check that the results are reproducible and consistent, therefore making them significant
One protein I have been focusing on is p21; p21 is known to inhibit the cell cycle, that is: stop the cell from dividing and producing more cells.
However other studies have shown that small amounts are still required for the cell cycle to progress...so not too much but not too little
Some studies have shown that if high levels of this protein is present in tumour cells the cells will become apoptotic or in simpler terms suicidal.
My aims are then;
1. Investigating the regulation of p21 in response to iron chelator drugs
2. Other proteins involved in the regulation of p21 and this will be investigated by studying the p21 gene closely
3. Animal studies
4. This will help understand the role of iron in cancer and the regulation of p21, and the mechanism by which iron chelators have this inhibitory effect on tumour cells
A new approach to Pancreatic Cancer treatment – Dr Zaklina Kovacevic
Pancreatic Cancer is a highly aggressive cancer with a 95% Mortality rate. The only known cure is surgery, with only 20% of all patients being suitable for surgery. 80% of patients have more advanced cancer, spread to local lymph nodes and/or liver from where it spreads to the rest of the body.
Chemotherapy is the best option utilizing Gemcitabine, with the average increase in survival 3-5 months.
A New Molecular Target: NDRG1 is a protein that can affect pancreatic cancer progression. NDRG1 inhibits tumor growth and spread.
Iron Chelators are then Novel drugs that target iron in cancer cells. Iron is in high demand by cancer cells! Iron chelators also target NDRG1 and increase NDRG1! Gemcitabine does not!
Zaklina tested The Iron Chelator DpC and Gemcitabine in an animal model of pancreatic cancer. The Iron Chelator DpC completely inhibited tumour growth!!!
Conclusions & Future Studies: Novel Iron Chelators are a promising strategy for Pancreatic Cancer. The target is NDRG1 with the studies showing it to be more effective than Gemcitabine
Further development of Iron Chelators for Pancreatic Cancer treatment is then required with aims to establish safe and effective dose and to Elucidate other molecular effects. |