Organoids in drug screening

Organoid research has been an emerging filed in the past few decades since organoids have the potential to provide better cancer drug screening. While cell culture is important for determining whether a drug should advance to clinical trials, a study showed that only 3.4% of cancer-targeting drugs passed the clinical trials and were further approved for use in patient care (1,2).

In the past few years, several research studies have shown that organoids provide accurate and reliable drug screening systems. Specifically, positive correlation was shown between drug response of in vitro organoid and their response in vivo, both in mice and in humans With increasing cases of cancer, patient-derived organoids (PDOs) may hold as a model system to choose the most effective treatment options for individual patients (3,4).

Patient-derived organoids

One possibility for the generation of patient-derived organoids consists in mincing up the patient tissue and plating the cells in drops of solid jelly like substance such as Matrigel or basement membrane extract. These substances are obtained from solubilized basement membrane of mouse sarcoma, and consist, among others, of laminin, collagen, and proteoglycans. After that, nutrient-filled media is added around the drops to support cell growth into organoids. Currently, patient-derived cancer organoids have been established for liver cancer, prostate cancer, breast cancer, colon cancer and pancreatic cancer. In these contexts, organoids have been used in clinical trials to investigate drug responses (5,6,7).

REFERENCES :

1. Mittal R, et al. Organ-on-chip models: implications in drug discovery and clinical applications. J Cell Physiol. 2018;234:8352–80.

2. Gupta N, et al. Microfluidics-based 3D cell culture models: utility in novel drug discovery and delivery research. Bioeng Transl Med. 2016;1:63–81.

3. Baker K. Organoids provide an important window on inflammation in cancer. Cancers. 2018;10:15

4. Vlachogiannis G, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018;359:920–6.

5. Broutier L, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017;23:1424–35.

6. Rossi G, et al. Progress and potential in organoid research. Nat Rev Genet. 2018;19:671–87.

7. Sachs N, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell. 2018;172(373–386):e10.