Precision nanomedicine for breast cancer

A new type of targeted nanotherapy could help women with an aggressive form of breast cancer in which tumour growth is spurred on by a receptor protein called HER2¹. The early results, published in the Russian Journal of Bioorganic Chemistry, demonstrate a promising new class of custom-built medicines.

Several HER2-targeted therapeutics already exist to treat this type of breast cancer, which accounts for around 25% of all cases of the disease. Yet most HER2-expressing breast tumours, when exposed to these drugs, evolve ways to thwart the anti-cancer onslaught — so new treatment options for patients with HER2-positive breast cancer are needed.

Researchers from the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry (IBCh) in Moscow, Russia, have now designed a promising anti-HER2 therapeutic that combines nanotechnology, synthetic binding proteins and a cell-killing payload.

The drug strategy starts with a bacterial enzyme called barnase that chops up RNA molecules that cause the death of human cells. The toxic molecule is encased inside tiny fat bubbles, known as liposomes, on to which the researchers attach an artificial antibody-like protein that binds to HER2. This ‘designed ankyrin repeat protein’ (DARPin) ensures that barnase only gets delivered to cancer cells, while the liposomes protect the rest of the body from the drug’s ill-effects during its transit through the bloodstream.

In laboratory experiments, the engineered nanomedicine obliterated human breast cancer cells by targeting HER2. In subsequent studies the drug also blunted cancer growth in tumour-bearing mice.

“The use of targeted liposomes as a nanocarrier allows thousands of toxic protein molecules to be delivered to cancer cells,” explains Galina Proshkina, a member of the IBCh team who is leading the drug’s development. “At the same time, the stability of liposomal structures in the bloodstream can reduce side effects and increase the therapeutic index of the drug.”

Galina and her colleagues, led by Sergey Deyev, head of the IBCh Laboratory of Molecular Immunology, have focused on HER2 targeting, but mostly as a proof of concept. The team are now planning to evaluate the therapy’s efficacy and safety in additional animal models, and human clinical trials could follow.

As Galina points out, however, the central design concept can be modified to attack other types of cancers with all manner of different payloads. Swap in a different DARPin, for example, and the therapy will home in on other surface markers; change the warhead to an imaging agent, and you’ve got a precision diagnostic tool. It is a promising and versatile platform that could help address some of biggest needs in cancer treatment today.