Better response to radiation and antibodies from HPV positive and AurkA heterozygous squamous cell carcinoma cells

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.

Publication History

Publication Date:
18 April 2018 (online)