Prevention of cardiac side effects of cancer treatment

Summary

This project will investigate a novel drug combination therapy that has potential benefits in cancer treatment induced heart failure by targeting Na+-K+ pump function.

Supervisor(s)

Dr Chia-chi Liu, Professor Helge Ramussen

Research Location

North Shore - Kolling Institute of Medical Research

Program Type

Masters/PHD

Synopsis

Heart muscle damage and heart failure is a serious side effect of cancer treatments and it is not uncommon that life expectancy is limited by treatment-induced heart disease rather than the treated cancer. Of drugs that cause heart failure the anthracycline group is particularly important. They are very effective against many cancers but cause heart failure with an increase in risk as the total dose increases. Medications trialled for prevention have largely been ineffective and none are in common use. In a novel approach to reduce heart muscle damage we have developed a small protein molecule that greatly increases the sensitivity of cancer cells to the anthracycline doxorubicin (Dox) while its effect on heart cells is much less pronounced. The molecule was originally an experimental tool we made to study mechanistic details of how a family of membrane proteins named "FXYD" regulate the membrane sodium pump in heart cells. We subsequently realised that this molecular tool might eliminate a protective mechanism many cancer cells have against oxidative stress, including treatment-induced oxidative stress. We confirmed this in experiments on cultured cells. Our objectives are to reduce the size of the cancer-killing molecule and refine its properties. We will then examine if it enhances Dox's anticancer efficacy when given to mice with cancer without harming the heart. This would allow lower doses of Dox to be used and therefore reduce or eliminate risk of heart failure.

Additional Information

The candidate will gain experience in cellular physiology, molecular biology, animal handling and surgery, medical treatment strategies and development. Interested students are asked to apply for all available funding (eg. APA, UPA, Heart Foundation, Heart Research Australia etc.). The potential supervisors will help with this process.

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Keywords

sodium-potassium ATPase, Redox signalling, oxidative stress, Cancer, heart failure, drug treatment

Opportunity ID

The opportunity ID for this research opportunity is: 1902

Other opportunities with Professor Helge Ramussen