Peter Nygren’s projects on improving cancer therapy

The application of the ‘one treatment fits all patients’ principle means that many patients will get suboptimal treatment. In fact, for major tumour types such as breast cancer, colorectal cancer and lung cancer, the majority of patients treated will not benefit but may only experience side effects. From quality of life and economical aspects this is, of course, suboptimal health care.

There is now a new generation of anti-cancer drugs being introduced for routine clinical use, e.g. various types of drugs interfering with cell signalling. Unfortunately, only a small fraction of patients experience a good effect of these drugs. In addition, therapy using the new drugs is generally very expensive. It is therefore of great interest to develop laboratory tests that can predict treatment effects and that could be used for individualizing anti-cancer drug treatment.

Our research has two main objectives:

  • To improve the efficacy of currently available chemotherapy by providing predictive information that allows for optimal drug selection.
  • To identify new lead compounds with potentially improved efficacy.

Key elements in these efforts are the development and application of information-rich compound libraries, clinically relevant tumour model systems and high-throughput analytical capabilities. This is combined with large-scale genomic profiling methods and high-level bioinformatics expertise, in addition to expertise in clinical oncology.
 

On-going projects

Identification of small molecules with cytotoxic effects against colorectal cancer tumour cells with specific and clinically relevant mutations

   Equipment used for screening of
   drug libraries

Peter Nygren, Henning Karlsson, Sadia Hassan, Sharmine Mansoori

This is done by screening of drug libraries in colorectal cancer cell line models harbouring defined mutations. This is a collaborative project with Tobias Sjöblom, Dept of Immunology, Genetics and Pathology.

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. Manuscripts are in preparation. The project is performed in collaboration with Rolf Larsson and Mårten Fryknäs, Dept of Medical Sciences.

Testing mebendazole as an anticancer drug in advanced refractory gastrointestinal cancer

Peter Nygren, Malin Berglund

A phase 2a clinical trial of the anti-helmintic drug mebendazole as an anticancer drug in advanced refractory gastrointestinal cancer is in late planning phase with the study protocol almost finalized and a new preparation of mebendazole for use in the trial is under production. 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. 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.