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Polo-like kinase inhibitors for targeted therapy in adrenocortical carcinoma

Project Description

Adrenocortical carcinoma (ACC) is a rare cancer with a generally poor prognosis and partially unknown pathogenesis. Despite recent advances in terms of molecular prognostic markers and efforts to identify potential drug targets, the clinical outcome is still unfavourable and no effective targeted pharmacological treatments are available for patients with advanced stages.
PLK1 is a mitotic regulator overexpressed in several solid tumours and is also involved in epithelial-mesenchimal transition (EMT), tumour metastasis and therapeutic resistance. Pan-PLK and PLK1 selective inhibitors represent a promising therapeutic approach for cancer treatment, especially when used in combination with other anticancer drugs. Recently, PLK1-specific inhibition has been demonstrated to to reduce cell viability in ACC cell lines and in xenograft models (Bussey et al 2016).
Aim of the present study will be to investigate the potential role of PLK1 as predictive marker and drug tartget in ACC. To this end, we will:
1. Evaluate PLK1 and PLK4 mRNA and protein expression in a large series of human ACC samples and to correlate it with clinical outcome and response to pharmacological therapy
2. Test in vitro efficacy of PLK1 and PLK4 inhibition by siRNA and by different PLK inhibitors on different ACC cell models alone and in combination with other anti-cancer compounds.
According to the preliminary result, we will consider to test in vivo the efficacy of PLK inhibitors by using xenograft models.

Person Specification
Applicants should have a strong background in molecular biology and preferably in cancer cell culture.
They should have a commitment to translational medical research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in Medical Sciences, Biosciences or Cancer Biology.

Informal enquiries should be directed to Dr Cristina L Ronchi, email

To be considered for this studentship, please send the following documents to Viktorija Ziabliceva, email :
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.

Funding Notes

Self-funded applications only.


- Else T et al. Adrenocortical carcinoma. Endocr Rev. 2014 35:282-326
- Fassnacht M et al. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018 179:G1-G46
- Mohan DR et al. Therapeutic Targets for Adrenocortical Carcinoma in the Genomics Era. J Endocr Soc. 2018 2:1259-1274
- Fu Z, Wen D. The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis. Cancers. 2017 9(10)
- Liu X. Targeting Polo-Like Kinases: A Promising Therapeutic Approach for Cancer Treatment. Transl Oncol. 2015 8:185-95
- Bussey KJ et al. Targeting polo-like kinase 1, a regulator of p53, in the treatment of adrenocortical carcinoma.
Clin Transl Med. 2016 5:1
- Giordano TJ et al. Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res. 2009 15:668-76
- Lippert J, …, Ronchi CL. Targeted Molecular Analysis in Adrenocortical Carcinomas: A Strategy Toward Improved Personalized Prognostication. J Clin Endocrinol Metab. 2018 103:4511-4523

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