Drug Sensitivity and Resistance Testing (DSRT)

Our Drug Sensitivity and Resistance Testing (DSRT) platform allows doctors and researchers to test pharmacological dependencies of cancer cells.

In this film you can see how drug sensitivity testing, the process by which patient cells are examined experimentally for response in activity to various drugs, is done at the HTB unit of FIMM Technology Centre.

How DSRT works

Each cancer case is unique and cancer patients often fail to respond to standard therapeutic options. In such cases our clinical DSRT (cDSRT) assay can help doctors to identify the most effective therapy for each particular patient or save them from the hurdles of inefficient therapies.

In a standard cDSRT assay, cancer cells taken directly from a patient are purified and placed in multi-well plates, where each well contains one of 528 clinically approved or experimental cancer drugs at one of five different concentrations. Cell viability is measured after 72 hours and based on this the most potent drugs are identified. The method has been extensively validated and described in peer-reviewed journals (e.g. Pemovska T. et al. 2013; Pemovska T. et al. 2015).

Here is a typical workflow for DSRT:

HTB DSRT workflow

 

In the classical DSRT all cells in a well are evaluated as a single unit. We commonly evaluate cell viability by adding CellToxGreen reagent (Promega) at the time of cell seeding, which makes dying cells fluoresce in the green channel. In addition, at the end of the incubation period CellTiter Glow reagent (Promega) is added, which lyses all cells and releases cellular ATP leading to emitting luminescence signal proportional to the number of metabolically active (live) cells.  

In addition to the classical DSRT, our high throughput flow cytometry-based DSRT allows to evaluate drug responses at the population level. Here each cell in each well produces a data point for each marker/antibody. This is particularly useful for mixed cell populations such as blood. Find out more about FIMM flow DSRT here.

The chart below illustrates the differences between the classical and flow-based DSRT

FICAN 2018 DSRT scheme

 

DSRT for doctors and cancer patients

cDSRT is not yet part of the standard therapeutic approach in cancer treatment.

  • Patients should contact their doctor for initiation of cDSRT testing and interpretation of the results. 
  • Doctors should initiate cDSRT projects via relevant research groups at FIMM / University of Helsinki rather than HTB directly: e.g. Caroline Heckman's group for hematological cancers, Emmy Verschuren's group for lung cancers, Vilja Pietiäinen for ovarian, urological, and pediatric solid tumors.

 

DSRT for pharma companies

Pharma companies can use the DSRT assay to test their drugs candidates on the same patient's cancer cells that we use for cDSRT described above, which may be considered as a surrogate approach for clinical trials. The use of biobanked samples is also supported. In this setting, pharmaceutical companies do not only test the effects of their drug candidates on real patient samples, but also get a chance to compare their drugs with other drugs from our oncology collection.

Interested companies should contact a respective research group to set up such a study rather than HTB directly: e.g. Caroline Heckman for hematological cancers, Emmy Verschuren for lung cancers, Vilja Pietiäinen for ovarian, urological, and pediatric solid tumors.

 

DSRT for academic researchers

Academic researchers can benefit from DSRT in many different ways:

  • DSRT can be used as another chemical tool to study your cells of interest. Use our chemical compound panels to identify relevant molecular signaling pathways or response spectra related to a defined genetic modification or other properties of your cells.
  • Identify genetic markers of drug responses in primary tumors by comparing DSRT results with genome sequencing data routinely obtained for each primary tumor sample processed at FIMM. Contact us for information on relevant permissions required for data access.
  • Explore the DSRT database for drug response modeling and simulation studies. Contact us for information on relevant permissions required for data access.