Dataset Information

Definition of key mechanisms of multidrug resistance of head and neck tumors to chemo- and radiotherapy treatments. Identification of new individualized antitumor drugs (Ref. GC16173720CARR)

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed cancer worldwide, with an incidence of about 600,000 new cases per year, accounting for 1-2% of all cancer deaths worldwide. Current treatment for head and neck cancer includes taxol (docetaxel), platinum compounds (e.g. cisplatin or carboplatin) and the anti metabolite 5 fluorouracil (5 FU), either as single agents or in combination, and also radiotherapy. Response rates to these chemotherapeutic drugs range from 60 to 80%, however there are high rates of resistance, which often leads to locoregional recurrence and metastasis. The therapeutic dose of treatment needed (hormone therapy, radiotherapy or chemotherapy) is often too toxic for the patient to withstand. Therefore, our main objetive in this proyect is the identification of the molecular and cellular mechanisms involved in the acquisition of resistance to chemotherapy as currently key pieces for the discovery of new drugs that allow the development of effective therapies against HNSCC.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pharynx

DISEASE(S): Head And Neck Squamous Cell Carcinoma

SUBMITTER: Yoelsis Garcia-Mayea

LAB HEAD: Matilde Esther LLeonart Pajarin

PROVIDER: PXD020159 | Pride | 2020-11-12

REPOSITORIES: Pride

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Publications

TSPAN1: A Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance.

Garcia-Mayea Yoelsis Y Mir Cristina C Carballo Laia L Castellvi Josep J Temprana-Salvador Jordi J Lorente Juan J Benavente Sergi S García-Pedrero Juana M JM Allonca Eva E Rodrigo Juan P JP LLeonart Matilde E ME

Cancers 20201105 11

Sensitization of resistant cells and cancer stem cells (CSCs) represents a major challenge in cancer therapy. A proteomic study revealed tetraspanin-1 (TSPAN1) as a protein involved in acquisition of cisplatin (CDDP) resistance (Data are available via ProteomeXchange with identifier PXD020159). TSPAN1 was found to increase in CDDP-resistant cells, CSCs and biopsies from head and neck squamous cell carcinoma (HNSCC) patients. TSPAN1 depletion in parental and CDDP-resistant HNSCC cells reduced cel ...[more]

PMID: 33167355

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Project description:Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex-vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biological processes that could be targeted to overcome intrinsic resistance. Experimental design: We analyzed both micro- and messenger RNA expression in a large panel of HNSCC cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of laryngeal cancer patients. Results: MiRs, mRNAs and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial to mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of laryngeal cancer patients. Conclusions: These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pre-treatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors. Matched pairs of pre-treatment biopsies of 34 patients treated at The Netherlands Cancer Institute between 2002 and 2010. Patients with T2-3 laryngeal cancers, all treated with radiotherapy alone with a curative intent. The series was designed to be a matched cohort of 17 patients with local recurrences matched with 17 local cures. There were no significant differences between groups with and without local recurrence in age, gender, subsite, T-stage or treatment year.

			Action	DRS
	ANOVA.xlsx	Xlsx
	Cell-VH-OFFGEL-18uL-TMT.msf	Msf
	Cell-VH-OFFGEL-TMT.msf	Msf
	Post-HocCSCs.xlsx	Xlsx
	Post-HocRCDDP.xlsx	Xlsx