Timing of chemotherapy ‘key to cancer treatment success’

9 May 2014

A new cancer treatment that is able to destroy tumour cells by disarming their defences and then hitting them with a deadly dose of DNA damage has been developed by researchers from the Massachusetts Institute of Technology (MIT).

By using mice models, the research team was able to demonstrate that this double-hit therapy can dramatically shrink lung and breast tumours. The treatment relies on a nanoparticle that carries two drugs and releases them at staggered intervals.

Professor Paula Hammond, co-lead author of the new study, commented: "I think it's a harbinger of what nanomedicine can do for us in the future. 

“We're moving from the simplest model of the nanoparticle — just getting the drug in there and targeting it — to having smart nanoparticles that deliver drug combinations in the way that you need to really attack the tumour."

During chemotherapy treatment, doctors generally administer two different drugs in hopes that a multi-faceted attack will be more successful compared to using a single medicine. 

Timing is key

Existing research has already identified therapies that work well together and co-lead author professor Michael Yaffe has previously demonstrated that the timing of drug administration can influence the success of the treatment.

Professor Yaffe added: "It's like rewiring a circuit. When you give the first drug, the wires' connections get switched around so that the second drug works in a much more effective way."

According to the professor, cancer cells can be weakened by using the drug erlotinib, which turns off one of the pathways that promotes uncontrolled tumour growth. Once treated, these cells are vulnerable to the DNA damaging drug doxorubicin compared to when the medicines are administered simultaneously.

Erlotinib works by targeting a protein called the epidermal growth factor (EGF) receptor, which is found on tumour cell surfaces. In the US, the  Food and Drug Administration has approved its use for treating pancreatic cancer and some types of lung cancer. 

Doxorubicin is used to treat many different types of the disease, including leukaemia and lymphomas, as well as bladder, breast, lung, and ovarian tumours.

Using both these drugs together, but not simultaneously, has proved to be particularly effective against a type of breast cancer known as triple-negative. According to Breast Cancer Care UK, around 15 per cent of those diagnosed with an invasive form of the condition have triple-negative breast cancer. 

Professor Yaffe and his team saw this as an exciting finding, but he said: "The problem was how do you translate that into something you can actually give a cancer patient?"

Turning lab results into effective treatments

The professor teamed up with Paula Hammond, who is a chemical engineer that had designed several nanoparticles that could carry two drugs at once. 

Her research group then created a particle called liposomes - spherical spherical droplets surrounded by a fatty outer shell - to deliver both erlotinib and doxorubicin. One was carried in the molecule’s core and the other was embedded in its outer layer.

Professor Hammond concluded: "With a nanoparticle delivery platform that allows us to control the relative rates of release and the relative amounts of loading, we can put these systems together in a smart way that allows them to be as effective as possible." 

Posted by Edward Bartel


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