Why many breast cancer patients develop drug resistance

Washington DC: Researchers have discovered a possible reason for drug resistance in breast tumors.

HER2 membrane proteins play a special role in certain types of breast cancer: amplified levels of HER2 drive unrestricted cell growth. HER2-tailored antibody-based therapeutics aim to prevent cancer cell growth, but two-thirds of HER2 positive breast cancer patients develop resistance against HER2-targeting drugs. The reason for this is not yet understood.

Researchers now found out, that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 breast cancer cells. This small subpopulation may have self-renewing properties that are resistant to HER2-antibody therapy and thus able to seed new tumor growth.

The INM - Leibniz-Institute for New Materials, Saarbrucken and the German Cancer Research Center (DKFZ) in Heidelberg researchers used a new electron microscopy method called Liquid STEM. It allows nanoscale studies of intact cells in their native liquid environment.

Niels de Jonge, head of the Innovative Electron Microscopy group, said that they found out that HER2 dimers appeared to be absent from a small sub-population of resting SKBR3 cells.

Jonge noted "could such cells survive the therapy and then develop into a drug resistant cancer at a later stage?" adding that it thus seems to be of key significance to study this sub-population of cells with exceptional phenotype.

Their novel findings were obtained as a direct consequence of the high spatial resolution of Liquid STEM combined with its capability to study many intact cells in liquid, says de Jonge.

The study is published in Science Advances.