BERWYN, PA — Panavance Therapeutics Inc., a clinical-stage pharmaceutical company, announced the recent publication of positive preliminary data in a manuscript titled, “The effect of GP‑2250 on cultured virus‑negative Merkel cell carcinoma cells: preliminary results1,” in the peer-reviewed Journal of Cancer Research and Clinical Oncology.
The objective of the preclinical study was to investigate the effects of GP-2250 on Merkel cell polyomavirus (MCPyV)-negative MCC cells. Patients with MCPyV-negative MCC have a much lower 5-year survival rate than MCPyV-positive cancer.
Greg Bosch, Chairman and CEO of Panavance Therapeutics commented, “We are encouraged by these preclinical findings in this rare, aggressive form of skin cancer. These preliminary results demonstrating the effectiveness of GP-2250 on MCC represent the second neuroendocrine cancer in which GP-2250 has shown effectiveness, the other one being pancreatic neuroendocrine cancer.”
“To date, the effects of GP-2250 have been studied in malignant skin cancers such as MCC and cutaneous squamous cell carcinoma, however, this study is the first time a more in-depth evaluation of the anti-neoplastic effects of GP-2250 in virus-negative MCC cell lines was conducted. This study was able to show that GP-2250 has significant, dose-dependent cytotoxic effects on MCC cells as well as reduced cancer cell proliferation and migration. We are extremely encouraged by these results as they add to our growing body of data and further support our belief in the potential of GP-2250 as an important treatment of a broad range of cancers,” added Prof. Dr. med. Chris Braumann, Chief of General, Visceral & Vascular Surgery, University of Duisburg-Essen, Germany; Head of Molecular and Clinical Research at Ruhr-University of Bochum, Germany; and Scientific Advisor to Panavance.
A research team at St. Josef-Hospital, Ruhr-University Bochum, Germany with support from the Company, studied three cell lines (MCC13, MCC14.2, MCC26) which were exposed to different GP-2250 doses. GP-2250’s effects on cell viability, proliferation and migration were evaluated by means of MTT, BrdU, and scratch assays, respectively. Flow cytometry was performed for the evaluation of apoptosis and necrosis. Western blotting was implemented for the determination of AKT, mTOR, STAT3 and Notch1 protein expression.
Results of the study showed that cell viability, proliferation and migration decreased with increasing GP-2250 doses. Flow cytometry revealed a dose response to GP-2250 in all three MCC cell lines. While the viable fraction decreased, the share of necrotic and in a smaller amount the apoptotic cells increased. Regarding Notch1, AKT, mTOR and STAT3 expression a comparatively time- and dose-dependent decrease of protein expression in the MCC13 and MCC26 cell lines was observed. By contrast, Notch1, AKT, mTOR and STAT3 expression in MCC14.2 was scarcely altered or even increased by the three dosages of GP-2250 applied.
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