Department of Medical Sciences

Cancer Pharmacology and Computational Medicine

Cancer Pharmacology and Computational Medicine

At Cancer Pharmacology and Computational Medicine we combine high-throughput screening, drug repurposing, innovative cell models, primary patient derived cells and computational approaches to find new treatment alternatives. We are also hosting the In vitro and systems pharmacology facility of the SciLife drug discovery and development (DDD) platform.

Cancer Pharmacology (Professor Rolf Larsson, Professor  Peter Nygren, Associate Professor Mårten Fryknäs, Associate professor Joachim Gullbo)

Computational Medicine (Professor  Mats Gustafsson)

Equipment and compound libraries

The following equipment is available at the lab:

  • Echo 550 acustic dispenser
  • IncuCyte Zoom, FLR & HD
  • FlexStation3
  • SCARA analysis platform
  • Wes
  • BioMek 4000
  • Q Exactive mass spectrometer
  • Cellomics ArrayScan
  • EnSpire Multimode reader
  • MagPix multiplex reader
  • NucleoCounter NC-250

Chemical compound libraries

Number of compounds within brackets.

  • Lopac (1280)
  • Spectrum (2000)
  • Pharmakon (1600)
  • Selleckchem (1650)
  • Actiprobe (2000)
  • Maybridge hit kit (3000)
  • Chembridge diverse set (10000)
  • Enzo (800)

Cancer pharmacology - Drug repositioning

Drug repositioning

New strategies for drug discovery are needed. One such strategy is drug repositioning/repurposing, i.e. when a new indication for an existing drug is identified and explored. In this approach, known on-patent, off-patent, discontinued and withdrawn drugs with unrecognized cancer activity can be rapidly advanced into clinical trial for this new indication since much or all of the required documentation to support clinical trials can rely on previously published and readily available data. During the past years we have systematically screened several innovative model systems with focus on colorectal carcinoma and acute myelocytic leukemia using our library of annotated and clinically tested drugs. In this effort we have identified several potentially useful candidates for repositioning including the anti-parasitic drugs mebendazole, nitazoxanide and quinacrine. Current research activities are focused on identification of compounds with immunooncology properties. With new methodology being developed for screening for immune modulating activity we will use our in-house library of clinically used compounds for identification of new candidates for drug repositioning. Contact Rolf Larsson (Rolf.Larsson@medsci.uu.se), Mårten Fryknäs (marten.fryknas@medsci.uu.se) or Peter Nygren (peter.nygren@igp.uu.se) for more information.

Cancer pharmacology - High-throughput screening - in 3D

High-throughput screening – in 3D

Understanding how cells within tumors respond to drugs is a critical issue in anticancer drug development. Much of what we currently know about cancer, both in terms of treatment and underlying molecular mechanisms, has been learned through growing cancer cells in the laboratory. One major limitation of conventional cell culture is that cancer cells are grown in a single ‘two-dimensional’ layer. In such cultures all cells have unlimited access to nutrients and oxygen and they can grow very quickly. In real tumors, where blood vessels grow chaotically, not all of the cells have a steady inflow of nutrients and oxygen. As a consequence, within tumors there are regions where cancer cells are starved and divide slowly or do not divide at all, while managing to stay viable. They also become insensitive to standard chemotherapy, which mainly targets actively dividing cells. After the treatment has ceased, these surviving dormant cells can often resume growth. They are also believed to be one of the major causes of cancer relapse. Thus, there has recently been an increased interest in laboratory cell models that would incorporate not only dividing, but also quiescent cells and that would mimic tumors in patients more accurately. One way of achieving this is growing cancer cells in three dimensions (3D). 3D cultures are essentially small tumors, in which cells have limited supply of oxygen and nutrients. These models could be a useful tool in the hunt for new drugs that are toxic to dormant cancer cells. We have developed a platform for high-throughput screening in 3D cultures. The platform makes it possible to monitor both viability and gene-expression responses to drugs in thousands of 3D cultures in parallel. Using this approach, we have found that inhibitors of oxidative phosphorylation (OXPHOS) are toxic to dormant cancer cells, and that inhibition of cholesterol synthesis (statins) increases the effect. Contact Wojciech Senkowski (wojciech.senkowski@medsci.uu.se) or Mårten Fryknäs (marten.fryknas@medsci.uu.se) for more information.