First cancer organ biobank

Release date: 2015-05-12

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Using three-dimensional (3D) organs derived from tumors in cancer patients, the researchers nearly replicated some of the key features of the primary tumor. These "organ-like" cultures are suitable for large-scale drug screening to detect some genetic changes associated with drug sensitivity, paving the way for individualized treatment to improve the clinical outcomes of cancer patients. They published the study in the May 7 issue of Cell.

Until now, people have mainly used two-dimensional cell lines in culture dishes or screened for anticancer drugs in mouse models. More similar to cell lines than human tumors, and saving time and resources compared to mouse models, organelles provide researchers with a compromise between existing methods.

The first author of the paper, Dr. Hayley Francies of the Sanger Institute at the Wellcome Foundation, said: "Every tumor is different, even if they appear in the same organ. They are each composed of a mixture of cells carrying different mutations. These mutations It determines whether the treatment works effectively. We are pleased that the organ can replicate some of the characteristics of the patient's tumor. This provides us with a more realistic environment to test new and existing drugs, and to explore joints. therapy."

The author of the paper, Dr. Mathew Garnett of the Sangk Institute of the Wellcome Foundation, said: "This is the first time that a cancer-like organ (live biobank) has been derived from a patient's tumor. We believe this exciting The new tools will have the potential to change the way we develop and deliver cancer treatments, helping to shed light on the complex interactions between multiple genomic variations in tumors that determine whether a drug works."

In the new study, the researchers used 22 tumors from 20 colorectal cancer patients to develop 22 organoids, and subsequently sequenced the genomic DNA isolated from these cultures. The genetic mutations in these organophyte cultures are highly matched to the mutations in the corresponding tumor biopsy specimens and are consistent with previous large-scale colorectal cancer mutation analysis results. The results confirm that these cultures faithfully capture the genomic characteristics of the source tumor and the many genomic diversity associated with colorectal cancer.

To link drug susceptibility to some genetic changes, the researchers then screened for the response of these organs to 83 experimental drugs and approved cancer drugs. Given their different genetic profiles, these organoids show various sensitivities to drugs. In the process of validating this method, the researchers identified associations between previously reported specific mutations and specific drug resistance. These organoids also reveal a new gene-drug association, suggesting that a drug that inhibits porcupine protein will benefit some cancer patients carrying the RNF43 mutation.

Researchers say that the organ will eventually be used clinically to predict the patient's response to treatment. But before that, more research work is needed to accelerate and standardize the process of generating and testing organs. In the short term, organoids will likely drive the process of accelerating the development of new cancer therapies and reduce costs.

Hans Clevers, a senior author of the paper and a professor at the Hubrecht Institute, said: "Usually, there is a wide distance from the study of cancer therapy in cells to the completion of a successful patient test. Because of the easy manipulation of organs, we can answer many of us. The problem with cancer has narrowed this distance. Organs not only save time and resources, but we hope that one day they will also allow us to see how treatments can work in individual cancers."

Source: Biopass

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