In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-11-15)
Abstract:
Recent technical advances mean that miniature replicas of many tissues can be grown in the laboratory. These so-called organoids provide scientists with model systems that are not as limited as simple, two-dimensional sheets of cells growing in a petri dish, and less labor and resource intensive than studies using laboratory animals. In particular, organoids grown from tumor cells from cancer patients have been suggested as having numerous advantages over both laboratory-grown cancer cells and mice when it comes to testing potential new anticancer drugs. Mutations in a gene called KRAS are common in many types of cancer including colon cancer. Tumors with these mutations are difficult to treat and so far virtually all attempts to generate compounds that selectively interfere with the KRAS protein encoded by the mutant gene have failed. Instead, drugs that indirectly inhibit this protein’s effects by targeting other proteins in the same signaling pathway are currently being tested on patients. However, there is still a need for better ways to pre-test whether these drugs will be effective in humans without having to expose the patient to side effects or an ineffective drug. Now, Verissimo, Overmeer, Ponsioen et al. have tested clinically-used KRAS pathway inhibitors and drug combinations against normal colon organoids and colon cancer organoids derived from patients with colon cancer. Gene editing techniques were used to introduce KRAS mutations into some of the normal organoids grown from healthy tissue, and into cancer organoids grown from tumors that had a normal copy of the KRAS gene. In all cases, only those organoids with mutant forms of the KRAS gene were resistant to the treatments. Furthermore, when organoids with the KRAS mutation were treated with some combination therapies that are currently being tested in clinical trials, the tumors stopped growing but the tumor cells failed to die. Similar drug treatments on mice carrying human colon cancer organoids confirmed these results, which is in line with previous studies where tumor tissue from human patients was transplanted into mice. These findings show that collections of tumor organoids from multiple patients could help researchers to quickly identify and optimize targeted anticancer therapies before they are incorporated into clinical trials. In the future, clinical studies are needed to verify how accurately the testing of cancer drugs on organoids predicts whether the drug will or will not work in patients.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.18489.001
DOI:
10.7554/eLife.18489.002
DOI:
10.7554/eLife.18489.003
DOI:
10.7554/eLife.18489.004
DOI:
10.7554/eLife.18489.005
DOI:
10.7554/eLife.18489.006
DOI:
10.7554/eLife.18489.007
DOI:
10.7554/eLife.18489.008
DOI:
10.7554/eLife.18489.009
DOI:
10.7554/eLife.18489.010
DOI:
10.7554/eLife.18489.011
DOI:
10.7554/eLife.18489.012
DOI:
10.7554/eLife.18489.013
DOI:
10.7554/eLife.18489.014
DOI:
10.7554/eLife.18489.015
DOI:
10.7554/eLife.18489.016
DOI:
10.7554/eLife.18489.017
DOI:
10.7554/eLife.18489.018
DOI:
10.7554/eLife.18489.019
DOI:
10.7554/eLife.18489.020
DOI:
10.7554/eLife.18489.021
DOI:
10.7554/eLife.18489.022
DOI:
10.7554/eLife.18489.023
DOI:
10.7554/eLife.18489.024
DOI:
10.7554/eLife.18489.025
DOI:
10.7554/eLife.18489.026
DOI:
10.7554/eLife.18489.027
DOI:
10.7554/eLife.18489.028
DOI:
10.7554/eLife.18489.029
DOI:
10.7554/eLife.18489.030
DOI:
10.7554/eLife.18489.031
DOI:
10.7554/eLife.18489.032
DOI:
10.7554/eLife.18489.033
DOI:
10.7554/eLife.18489.034
DOI:
10.7554/eLife.18489.035
DOI:
10.7554/eLife.18489.036
DOI:
10.7554/eLife.18489.037
DOI:
10.7554/eLife.18489.038
DOI:
10.7554/eLife.18489.039
DOI:
10.7554/eLife.18489.040
DOI:
10.7554/eLife.18489.041
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
Bookmarklink