Peter Nygren’s projects on improving cancer therapy
Identification of new drugs that could act synergistically with radiotherapy
Peter Nygren, Henning Karlsson
In this project we investigate interactions between the cytotoxic effects of small molecules and radiation. Candidate drugs, VLX600 and nitazoxanide, have been identified and further analysed in 2D and 3D tumour models as well as in xenograft studies in vivo. The project is performed in collaboration with Rolf Larsson and Mårten Fryknäs, Dept of Medical Sciences.
Development of mebendazole as an anticancer drug in advanced refractory gastrointestinal cancer
Peter Nygren, Malin Berglund, Sharmineh Mansori
A phase 2a clinical trial of the anti-helmintic drug mebendazole as an anticancer drug in advanced refractory gastrointestinal cancer has recently been finished and study data are to be presented. The project is based on a pilot study that showed a significant activity of mebendazole in this setting. In parallel, the mode of action of mebendazole as an anticancer drug has been investigated and will be reported. Since mebendazole has poor bioavailability a prodrug will be synthesized to allow for improved pharmacokinetics and thus efficacy. The project is performed in collaboration with Rolf Larsson and Mårten Fryknäs, Dept of Medical Sciences.
Characterisation of cytotoxic effects of new potential drugs
Peter Nygren, Henning Karlsson, Sadia Hassan, Sharmine Mansoori
Since several years we have been working with an in-house developed short-term in vitro assay for patient tumour cells, the fluorometric microculture cytotoxicity assay (FMCA), which has been shown to report clinically relevant drug activity data in major cancer types. In this project we use the FMCA of the tumour cell to characterise cytotoxic effects of drugs identified in drug repurposing screens in patient tumour samples representing a spectrum of sensitivity to standard drugs. The aim is to identify the tumour diagnoses suitable for future clinical development of these drugs into anticancer drugs.
Development of phenotypic cancer drug activity screen in tumour organoids for individualized treatment
Peter Nygren, Henning Karlsson
We have extensive experience from cancer drug activity testing in primary cultures of tumour cells from patients as a basis for individualized selection of drugs for treatment. One problem with this technique is that the number of cells available for testing might be too small for extensive testing and another that test results might not apply when the patient experience tumour relapse or progression after one or several lines of therapy.
In this project the tumour cells are cultured to expand and form tumour organoids being reminiscent of the tumour allowing for expanded testing. Furthermore, by exposing the organoids with the drugs that are included in the patient treatment prior to drug testing, the results might be more applicable at the time when a new treatment is to be decided. The project is performed in collaboration with Claes Andersson and Kristin Blom, Dept of Medical Sciences.