Primary tumor cells open up improved cancer treatment
A Hannover – German researchers have made a significant step forwards towards a more individualized, specific treatment, diagnosis, and prognosis of breast cancer. For the first time, researchers under Professor Ralf Hass from the Hannover Medical School (www.mh-hannover.de/4122.html) were able to isolate breast cancer cells directly from tumor biopsies. Even after two years of cultivation the cells proliferate at “an incredibly high rate”, according to Hass, and show the characteristics of primary breast cancer cells.
“Our cell cultures as well as cell-based assays designed on this basis open up an avenue to develop breast cancer treatments which are more specific than the current chemotherapeutic gold standards”, says Hass, who has applied for a patent on his groundbreaking technology. “Currently, doctors have to balance the therapeutic effect of non-specific breast cancer drugs such as taxanes or anthracyclins with their severe side effects”, notes Hass. “Consequently, tumor destruction often remains incomplete, leading to minimal residual disease, development of drug resistance and tumor relapses. This may be one reason for the high mortality rates from breast cancer.”
Complete product pipeline
To combat this, Hass plans to develop a complete diagnostic, prognostic and therapeutic product pipeline for breast cancers, together with partners from the bio-pharmaceutical and diagnostics industry. “Furthermore, we will be looking for funding and will possibly spin-out a company on our own”, Hass told EuroBiotechNews. “Our primary breast cancer cells, which remain tumorigenic and proliferative even after cryo-conservation, offer multiple options: from biomarker identification and drug susceptibility testing to multiplex-screening of drug effects in human cell culture,” says Hass. “All published methods so far use extracellular matrix proteases to release breast cancer cells from biopsies. However, our biochemical and videomicroscopic data indicate that those cells lose their ability to grow autonomously as a result of this treatment. By avoiding this step we are in the unique position of being able to scale up tumorigenic cells with features very close to the in vivo situation.
Most of the current work to be published soon is on the characterization of the primary cultures and on the optimization of culture conditions. The clinicians are currently cultivating tiny blocks of tumor cell material of 1mm3 in serum-free medium at pH7.4 and 300 mosmol/kg. According to Western blots and FACS analysis there has been no contamination by lymphocytes, fibroblasts, myoepithelial or other cells. The epithelial mammacarcinoma cells are Desmin–, CD45– and do not express Prolyl-4-hydroxylase. Their capacity for continuous proliferation is monitored by the incorporation of [3H]-Thymidin and was confirmed by PCR-based telomerase assays.
Hass is now planning to optimize his patient-specific assay system, is looking for bio-markers that can differentiate breast cancer from metastatic cells, and will be scrutinizing the factors that determine drug resistance. “We must be realistic, “ he says. “this challenge requires an interdisciplinary collaboration with strong partners.”B