Vilgelm Laboratory - Abstract 5602: Molecular mechanism underlying

Journal article

A. Vilgelm, Yan Liu, S. Levy, A. Richmond
2012

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APA Click to copy
Vilgelm, A., Liu, Y., Levy, S., & Richmond, A. (2012). Abstract 5602: Molecular mechanism underlying acquired resistance to Aurora A kinase inhibitor, Alisertib, in melanoma.

Chicago/Turabian Click to copy
Vilgelm, A., Yan Liu, S. Levy, and A. Richmond. “Abstract 5602: Molecular Mechanism Underlying Acquired Resistance to Aurora A Kinase Inhibitor, Alisertib, in Melanoma” (2012).

MLA Click to copy
Vilgelm, A., et al. Abstract 5602: Molecular Mechanism Underlying Acquired Resistance to Aurora A Kinase Inhibitor, Alisertib, in Melanoma. 2012.

BibTeX Click to copy

@article{a2012a,
  title = {Abstract 5602: Molecular mechanism underlying acquired resistance to Aurora A kinase inhibitor, Alisertib, in melanoma},
  year = {2012},
  author = {Vilgelm, A. and Liu, Yan and Levy, S. and Richmond, A.}
}

Abstract

Malignant melanomas are notorious for their resistance to chemotherapeutic treatments. Thus the development of new therapeutic strategies that will allow overcoming drug resistance is essential. We have previously shown that Aurora A kinase (AurkA) inhibitor Alisertib (MLN8237) inhibited melanoma cell grouth by blocking mitosis and inducing senescence. In this study we used melanoma patients’ tissue specimens implanted under the skin of athymic mice and mouse melanoma tumors grown in immune-competent mice. Treatment with Alisertib inhibited melanoma tumor growth in both model systems. However, most of tumors re-grew after the treatment was paused and some of them acquired resistance to a second round of chemotherapy. Interestingly mouse melanoma cells collected from chemo-resistant tumors retained their resistance to Alisertib treatment when re-implanted into new hosts. In order to gain understanding of the molecular events facilitating Alisertib resistance we performed whole transcriptome sequencing in mouse melanoma tumors. Each Alisertib-treated tumor showed a large number of genomic alterations with the number of single nucleotide variations in protein-coding transcripts ranging from 807 to 2036. In total 613 genes were affected across 6 analyzed samples and among those, 253 genes carried nucleotide variations exclusively in drug resistant tumors. In silico pathway analysis revealed a statistically significant enrichment of this resistance-associated gene set with genes involved in cell cycle regulation (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5602. doi:1538-7445.AM2012-5602