A new study demonstrates the use of 3D cancer cultures called organoids in personalized drug screening.
Cultures grown from patients’ cancer tumors mimic key aspects of the originals, according to a new study published in the journal, Cell.
Researchers refer to these cultures as organoids, and are using them to test how a patient’s tumor might change in the presence of certain anti-cancer medications.
The ways in which patients react to specific treatment varies by individual; and it is believed that each tumor inside a patient is different. Organoids can be useful in detecting drug-related genetic changes, and have the potential to usher in a new era of personalized cancer treatments.
Senior study author Mathew Garnett, from the Wellcome Trust Sanger Institute states:
This is the first time that a collection of cancer organoids, or a living biobank, has been derived from patient tumors. We believe that these organoids are an important new tool in the arsenal of cancer biologists and may ultimately improve our ability to develop more effective cancer treatments.
Every tumor is unique
One of the challenges of treating cancer is that each tumor has its own “unique spectrum of genetic mutations,” according to the press release. Garnett says in a Sanger Institute video (embedded below), “we want models that really reflect the disease accurately.”
Scientists use cancer cell models to mimic patient tumors in their effort to study the causes of cancer and search for potential new treatments. Before the organoids, the experimental cells (known as cell lines) were typically housed on two-dimensional slides. The cell lines do not always reflect important features of tumor cells that may impact the efficacy of treatments.
Organoids are a new approach to determining how tumors might react to medications. In this alternative approach to the petri dish-grown cell lines, organoid cell culture systems are grown from stem cells taken from the tumors of colorectal cancer patients.
These three-dimensional organoids maintain the hallmarks of the tissue from which they were grown. The cell types present in organoids, and their ability to self-renew, make them much more realistic examples of a patient’s tumor.
In this most recently published organoid study, an international collaboration of researchers from the Sanger Institute in the UK, the Hubrecht Institute in the Netherlands, and Harvard University in the US, sampled tumor tissues from 20 patients with colorectal cancers from which they grew 22 organoids. After sequencing the genomic DNA of the cultures, Garnett and Clevers found that the genetic mutations in the organoid cultures were a good match to those found in the tumor biopsies. The mutations were also in line with prior studies, according to the authors.
The next step: drug trials on organoids
Garnett and Clevers then set out to test the oraganoids to see how their specific genetic mutations might respond to 83 experimental and approved cancer drugs. Given the genetic diversity of the organoids, they found a range of sensitivities to the drugs. To validate their approach, researchers compared their results to those of previously reported drug resistance in specific mutations. They found that a porcupine protein-inhibiting drug would greatly benefit the subset of colorectal cancer patients with RNF43 mutations.
Image credit: van de Wetering et al./Cell 2015
Personalized cancer treatment: We’re not there yet
What’s most remarkable to me about this research is just how diverse and individualized cancer can be. Even within one tumor, there can be a variety of genetic mutations that respond differently to cancer drugs. If you consider nearly 1.4 million cases of colorectal cancer were diagnosed, globally, in 2012, researchers have a great deal of variability to take into account as they progress toward personalized cancer treatment. According to Garnett:
At some point in the future, this approach may be suitable for modeling individual patient response to cancer therapies to inform clinical treatment.
In the video, researcher Haley Francies of the Wellcome Trust Sanger Institute, says:
Personalized cancer treatments have led to advancements in a large number of cancers; however, the problem with these treatments is that they usually only have this great response in a small number of patients.
Given the numerous differences in individual cancer cell mutations, the researchers need to expand their organoid farm, and also begin to develop organoids for other types of tumors.
The nuviun blog is intended to contribute to discussion and stimulate debate on important issues in global digital health. The views are solely those of the author.