News Column

Studies from F. Mouawad and Colleagues Reveal New Findings on Head and Neck Cancer

February 12, 2014



By a News Reporter-Staff News Editor at Biotech Week -- Current study results on Oncology have been published. According to news reporting originating in Toulouse, France, by NewsRx journalists, research stated, "Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer world-wide. The treatment of advanced stages HNSCC is based on surgical treatment combined with radiotherapy and chemotherapy or concomitant chemo-radiotherapy."

The news reporters obtained a quote from the research, "However, the 5-year survival remains poor for advanced stages HNSCC and the development of new targeted therapies is eagerly awaited. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. This spermine moiety facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and reinforces topoisomerase II poisoning. Here we report the evaluation of F14512 toward HNSCC. Four cell lines representative of head and neck cancer localizations were used: Fadu (pharynx), SQ20B (larynx), CAL33 and CAL27 (base of the tongue). PTS activity and specificity were evaluated by confocal microscopy and flow cytometry using the fluorescent probe F17073 which contains the same spermine moiety as F14512. Cytotoxicity, alone or in association with standard chemotherapeutic agents (cisplatin, 5FU), and radio-sensitizing effects were investigated using MTS and clonogenic assays, respectively. F14512 efficiency and PTS activity were also measured under hypoxic conditions (1% O-2). In all 4 tested HNSCC lines, an active PTS was evidenced providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Interestingly, F14512 presents a 1.6-11-fold higher cytotoxic effect than the reference compound etoposide (lacking the spermine chain). It appears also more cytotoxic than 5FU and cisplatin in all cell lines. Competition experiments with spermine confirmed the essential role of the PTS in the cell uptake and cytotoxicity of F14512. Hypoxia had almost no impact on the drug cytotoxicity. The combination of F14512 with cisplatin, but not 5FU, was found to be synergistic and, for the first time, we demonstrated the significant radio-sensitizing potential of F14512. The spermine moiety of F14512 confers a targeted effect and a much better efficacy than etoposide in HNSCC lines."

According to the news reporters, the research concluded: "The synergistic effect observed in association with cisplatin and radiotherapy augurs well for the potential development of F14512 in HNSCC."

For more information on this research see: The antitumor drug F14512 enhances cisplatin and ionizing radiation effects in head and neck squamous carcinoma cell lines. Oral Oncology, 2014;50(2):113-119. Oral Oncology can be contacted at: Elsevier Science Bv, PO Box 211, 1000 Ae Amsterdam, Netherlands. (Elsevier - www.elsevier.com; Oral Oncology - www.elsevier.com/wps/product/cws_home/105)

Our news correspondents report that additional information may be obtained by contacting F. Mouawad, Res & Dev Center Pierre Fabre, Toulouse, France. Additional authors for this research include A. Gros, B. Rysman, C. Bal-Mahieu, C. Bertheau, S. Horn, T. Sarrazin, E. Lartigau, D. Chevalier, C. Bailly, A. Lansiaux and S. Meignan (see also Oncology).

Keywords for this news article include: Antineoplastics, Pharmaceuticals, Drugs, France, Europe, Toulouse, Oncology, Cisplatin, Etoposide, Treatment, Chemotherapy, Radiotherapy, Alkylating Agents, Chlorine Compounds, Mitotic Inhibitors, Nitrogen Compounds, Platinum Compounds, Head and Neck Cancer, Squamous Cell Carcinoma

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Biotech Week


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