Since accurately picking drugs to fight patients’ unique tumor mutations remains in large part a guessing game, researchers have been working on finding better approaches. An international team of investigators has developed a way of growing living organoids from patients’ own tumor cells for use as a testing platform to discover which drugs work before trying them directly on the patients.
Organoids resemble the original tumors much better than cell lines, having a 3D structure, a variety of cells, and similar growth characteristics. In the study published in journal Cell, the researchers grew organoids from colorectal cancer biopsies taken from 20 patients. They sequenced the DNA of the organoids as well, as well as the original tumors, comparing how the pairs change over time. They discovered that similar mutations occur in the cancers and their corresponding organoids, pointing to the use of organoids as an accurate platform for drug selection.
Some details from the study abstract:
In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely recapitulate several properties of the original tumor. The spectrum of genetic changes within the “living biobank” agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than inAPC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell-line- and xenograft-based drug studies, and allow personalized therapy design.
Study in journal Cell: Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients…
Source: Cell Press…