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THE MOUSE HOLLOW FIBRE MODEL IN CANCER DRUG DISCOVERY

The main objective in cancer drug discovery programs is to rapidly identify lead compounds that have promising pharmacokinetics (PK) and pharmacodynamics (PD) (efficacy). However, screening of compounds for efficacy in animal models of cancer (xenograft and orthotopic models) takes approximately a month. Secondly, PK and PD studies are performed in different animals. Thirdly, efficacy is studied against different cell lines in different groups of animals

The hollow fibre (HF) model in mice provides a platform to rapidly screen anti-cancer compounds simultaneously for PK and efficacy against multiple cell lines to identify promising compounds for proof of concept studies in xenograft models. Efficacy in Hollow Fibre models has been shown to be predictive of efficacy in Xenograft models.

Advantages
  1. 1. Short duration of model – 1 week
  2. 2. PK and Efficacy determined simultaneously in single animal
  3. 3. Single compound screened against multiple cancer cell lines in single animal.
  4. 4. Rapid identification and prioritization of lead compounds for xenograft POC studies.
  5. 5. Reduction of animals, time and cost to identify lead compounds.

TheraIndx Lifesciences has established and validated the HF model. This model can be used to quickly screen promising anti-cancer compounds for PK/PD and prioritisation for Proof of concept studies in Xenograft models.

    References:
  • 1. Johnson JI, Decker S, Zaharevitz D, Rubinstein LV, Venditti JM, Schepartz S, Kalyandrug S, Christian M, Arbuck S, Hollingshead M, Sausville EA.2001. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 18;84(10):1424-31.

  • 2. Casciari JJ, Hollingshead MG, Alley MC, Mayo JG, Malspeis L, Miyauchi S, Grever MR, Weinstein JN. 1994. Growth and chemotherapeutic response of cells in a hollow-fiber in vitro solid tumor model. J Natl Cancer Inst.86(24):1846-52.