Introduction:
Chordomas are rare, malignant primary tumors of the bone, which are supposed to arise
from the rests of the chorda dorsalis along the spine. Clival chordoma are interfere
with ENT and are operated in an interdisciplinary approach. Due to the generally slow
proliferation rate of chordomas, these tumors have low response rates to conventional
chemotherapy. Therefore new therapeutical options based on targeted therapy are needed.
Material and Methods:
We established a chordoma collective with 43 patients and characterize 6 stable chordoma
cell lines. The cell lines were characterized by means of mRNA-microssay and western
blot analysis. The collective was defined through immunohistochemical staining. After
that we performed an inhibition test with a CDK4/6 inhibitor palbociclib. The growth
inhibition was detected by western blot, cell cycle analysis and MTS cell viability
assays.
Results:
The chordomas of the collective and the cell lines showed a recurrent loss of CDKN2
and a loss of p16 protein expression over 90%. This leads to a constitutively active
p16 cascade, loss of control of the cyclin depended kinases CDK4/6 and an active cell
cycle. We are able to show that palbociclib as a specific CDK4/6 inhibitor significantly
inhibits growth in several chordoma cell lines in vitro. Over 85% of the patients
in the collective present a potential immunohistochemical „responder phenotype” for
a possible therapy with palbociclib.
Conclusion:
Due to this data a clinical trial under the guidance of the NCT in Heidelberg (Prof.
Schlenk/Prof. Fröhlich) will be launched this year (NCT03110744) in Germany.
