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Using 3D cell cultures to fight anti-cancer therapy resistance

Date:
December 11, 2017
Source:
University of Bern
Summary:
An international research team has developed 3D cell cultures in which genes can be specifically modified. They allow the study of genes that may cause therapy resistance in breast cancer. This knowledge may further improve the use of targeted anti-cancer drugs.
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An international research team headed by the University of Bern and the Netherlands Cancer Institute has developed 3D cell cultures in which genes can be specifically modified. They allow the study of genes that may cause therapy resistance in breast cancer. This knowledge may further improve the use of targeted anti-cancer drugs.

Drug resistance remains the major cause of death of patients suffering from metastasized cancer. Unfortunately, there is no ideal therapy that suits all patients. Moreover, the most efficient therapy should be used right from the start to increase the chance of cure and to minimize the risk of drug resistance. Therefore, an important goal in modern cancer research is the development of individualized therapies for cancer patients, the so-called precision medicine. In close collaboration with the Netherlands Cancer Institute (NKI) in Amsterdam and the Hubrecht Institute in Utrecht, a research team at the University of Bern has generated 3D cell cultures (so-called organoids) to investigate mechanisms of drug resistance in breast cancer and to improve current therapy. The corresponding article was just published in Nature Methods.

Targeted analyses using molecular scissors

How to identify the best therapy for an individual patient? "We are studying whether so-called organoids are useful to elucidate mechanisms of therapy resistance and to predict therapy response," says Sven Rottenberg from the Vetsuisse faculty of the University of Bern. For this purpose, the scientists are culturing the tumor cells in a three-dimensional matrix and complement the culture medium with special growth factors. Using the molecular scissors CRISPR/Cas9, specific genes in these 3D cell cultures can be modified to investigate the effect on therapy response. This approach may be useful to mimic therapy response of patients and to find the optimal therapy in vitro.

A possible alternative to animal experiments

In contrast to classical cell cultures, organoids have major advantages, explains Sven Rottenberg: "This method opens new possibilities, since 3D organoids grow much more efficiently in the Petri dish -- and they keep special features as well, including the typical cellular heterogeneity of cancer." This is unlike the few selected tumor cells that grow under conventional cell culture conditions and often do not represent the original tumor anymore. The hope is that this approach replaces the cumbersome transplantation of human tumor fragments into mice. "This would reduce the number of complex animal experiments," adds Rottenberg. Nevertheless, he also sees work ahead: "Regarding therapy response we see in our model that not all organoids tested in vitro predict the real in vivo response correctly. For some tumors, we are still missing factors that influence drug response and that cannot be modelled sufficiently with the current organoid approach." The research group of Sven Rottenberg is working on further optimizing the cell culture conditions to put the puzzle of drug resistance mechanisms together.


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Materials provided by University of Bern. Note: Content may be edited for style and length.


Journal References:

  1. Norman Sachs, Joep de Ligt, Oded Kopper, Ewa Gogola, Gergana Bounova, Fleur Weeber, Anjali Vanita Balgobind, Karin Wind, Ana Gracanin, Harry Begthel, Jeroen Korving, Ruben van Boxtel, Alexandra Alves Duarte, Daphne Lelieveld, Arne van Hoeck, Robert Frans Ernst, Francis Blokzijl, Isaac Johannes Nijman, Marlous Hoogstraat, Marieke van de Ven, David Anthony Egan, Vittoria Zinzalla, Jurgen Moll, Sylvia Fernandez Boj, Emile Eugene Voest, Lodewyk Wessels, Paul Joannes van Diest, Sven Rottenberg, Robert Gerhardus Jacob Vries, Edwin Cuppen, Hans Clevers. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell, 2017; DOI: 10.1016/j.cell.2017.11.010
  2. Alexandra A Duarte, Ewa Gogola, Norman Sachs, Marco Barazas, Stefano Annunziato, Julian R de Ruiter, Arno Velds, Sohvi Blatter, Julia M Houthuijzen, Marieke van de Ven, Hans Clevers, Piet Borst, Jos Jonkers, Sven Rottenberg. BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance. Nature Methods, 2017; DOI: 10.1038/nmeth.4535

Cite This Page:

University of Bern. "Using 3D cell cultures to fight anti-cancer therapy resistance." ScienceDaily. ScienceDaily, 11 December 2017. <www.sciencedaily.com/releases/2017/12/171211122820.htm>.
University of Bern. (2017, December 11). Using 3D cell cultures to fight anti-cancer therapy resistance. ScienceDaily. Retrieved October 4, 2024 from www.sciencedaily.com/releases/2017/12/171211122820.htm
University of Bern. "Using 3D cell cultures to fight anti-cancer therapy resistance." ScienceDaily. www.sciencedaily.com/releases/2017/12/171211122820.htm (accessed October 4, 2024).

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