Introduction:
The EGFR antibody cetuximab is used in patients with squamous cell carcinoma of the
head and neck (HNSCC), but in some cases with considerable side effects. In preliminary
work, we were able to show that only HNSCC cell lines with a heterozygous allele of
the Aurora Kinase A (AurkA) Phe31Ile polymorphism respond to cetuximab therapy. The
aim of this work was to identify further therapeutic predictors for the response to
cetuximab.
Method and material:
The proliferation behavior of three HPV-negative and three HPV-positive HNSCC cell
lines with different AurkA polymorphism was investigated after treatment with the
cytostatic drugs cisplatin and 5-FU as well as after administration of the antibodies
cetuximab and gefitinib in combination with irradiation using the Crystal-Violet-Proliferation
assay. The migration tendency was investigated by means of the wound-healing assay
and the invasion behavior by invasion-chamber.
Results:
We found that HPV positive and AurkA heterozygous cells showed the best response to
cytostatic drugs, antibodies and radiotherapy. The known radiation-induced migration
could be inhibited most strongly in these cells by cytostatics/antibodies. This was
also found for the invasiveness.
Summary:
The results show that HPV positive cells simultaneously displaying the heterozygous
polymorphism have a good response to radiation and cytotoxic/antibody treatment.