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Patient Derived Xenograft (PDX) Models

In cancer drug discovery, Xenograft models in mice are routinely used to test efficacy (anti-cancer activity) of anti-cancer compounds. Human cancer cells are injected sub-cutaneously into immunologically deficient mice and allowed to form tumours and then treated with preclinical candidate drugs for two to three weeks. Efficacy is measured as the ability of the compound to reduce the tumor growth. Compounds with the best efficacy are progressed to preclinical development and clinical trials. Despite its widespread use the xenograft model is a poor predictor of efficacy in cancer patients because of which more than 90% of drugs fail in late stage clinical trials. The main reason for this is the cancer cell lines used in xenograft models do not represent the characteristics of cancer cells observed in patients.

The PDX model has been developed to overcome this limitation. In PDX models, cancer cells or tissues are taken from patients, implanted into mice followed by treatment with clinical candidate drugs.

Advantages
  1. 1. Representative of human cancers
  2. 2. High translation of efficacy to humans
  3. 3. Reduction in failure rates
Disadvantages
  1. 1. Difficult to establish
  2. 2. Availability of human tissues
  3. 3. Time consuming

TheraIndx Preclinical CRO, Bangalore has established both xenograft and PDX models representing many cancer types. This can help in improving the success of preclinical drug candidates.

    References:
  • 1. Sharpless, NE and DePinho, RA. 2006. Mouse xenograft models vs GEM models for human cancer therapeutics. Nature Reviews Drug Discovery | AOP, published online doi:10.1038/nrd2110

  • 2. Williams. J.A. 2018. Using PDX for Preclinical Cancer Drug Discovery: The Evolving Field. J. Clin. Med. 7, 41; doi:10.3390/jcm7030041