Aurora kinase A inhibition as a promising therapeutic strategy in ARID1A-mutated neuroendocrine carcinomas: First results of an in vitro and in vivo study

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Introduction: Neuroendocrine carcinomas of the gastrointestinal tract (GEP-NEC) are rare but extremely aggressive tumor diseases with a 5-year survival rate of approximately 25%. The inactivating ARID1A mutation can be detected in approximately 40% of cases of GEP-NEC. Previous studies have shown that Aurora kinase A inhibition leads to selective synthetic lethality of ARID1A-deficient colorectal tumor cells.

Aim(s): Since there is currently no established targeted therapy for GEP-NEC, Aurora kinase A inhibition in ARID1A-mutated GEP-NEC is being investigated as a new mutation-based targeted therapy.

Materials and methods: The newly established ARID1A-mutated GEP-NEC cell line NT-38 was treated with the Aurora kinase A inhibitor Alisertib. Here, proliferation and apoptosis induction were investigated. Subsequently, the response to Alisertib was verified in a subcutaneous and orthotopic NT-38 xenograft model.

Conference:

Presenting Author:

Authors: Viol F, Amin T, Sipos B, Fründt T, Smolkova B,

Keywords: Neuroendocrine Carcinoma, Mutation based Therapy, ARID1A, Aurora Kinase A,