Tag: cancer cell lines

Categories : Cancer NeurologyTags :

A Living Biobank of Brain Metastasis Samples will Unlock New Research

On By ModernMedia
Photo by National Cancer Institute on Unsplash

At 18 Spanish hospitals, when a patient with brain metastasis undergoes surgery, they can donate a tiny part of their brain to the first repository of brain metastasis living samples in the world, based at the Spanish National Cancer Research Centre (CNIO). A world-first collection, it was created to accelerate the search for therapies against brain metastasis, a disease that affects up to 30% of patients with systemic cancer.

The creators of this repository, called RENACER (Spanish acronym for the National Brain Metastasis Network), are two CNIO researchers, Manuel Valiente, head of the Brain Metastasis Group, and Eva Ortega-Paíno, director of the Biobank. They explained the advantages of the collection in the journal Trends in Cancer. In just three years RENACER has compiled samples from more than 150 patients.

The truly unique feature of RENACER, which makes it a valuable tool for the international scientific community, is that it contains living samples, conserved in cultures that enable the cells to continue behaving in a similar way as they were in the body.

A living biobank that enables organotypic cultures

“We have built a ‘living’ biobank” write Valiente and Ortega-Paíno. And this characteristic can be “transformative, not only for research but also for clinical trial design, especially when focused on unmet clinical needs, such as brain metastasis”.

The fact that the cells are living allows them, for example, to study their response to specific drugs. RENACER paves the way to create avatars for each patient in order to identify the best therapeutic options in an individualised way.

“Research contracts have been already signed to exploit patient-derived organotypic cultures (PDOCs) as avatars, thus providing the possibility to generate biomarkers of sensitivity or resistance to specific drugs” the authors explain.

The hospitals involved with RENACER work as a network to pass on research findings to patients as quickly as possible. In fact, thanks to this network, there are already two clinical trials underway, which will determine the capacity of two biomarkers to discriminate cases in which radiotherapy – a technique with side effects – will be effective.

From the operating theatre to the biobank in hours

The requirement for cells to be “alive” is not easy to achieve, since it involves a sophisticated logistics chain. The samples are taken from the operating theatre in a special container, in their culture medium, at a temperature of between 4 and 8 degrees centigrade.

They must reach the CNIO Biobank, in Madrid, in less than 24 hours. There, they are processed, organotypic cultures are created, and they are divided into proportional parts that are stored as samples for future investigations. They are also analysed using various techniques and sequenced, to extract as much information as possible from them. All the data are put into a database that is open to the international scientific community.

“It is pivotal to empower patients”

“This is happening just a few years after the project was launched,” said Valiente. “It’s a strategy that helps to improve knowledge as well as diagnosis and treatment options, but also brings all the people involved closer together: patients, core researchers, chemical re searchers, healthcare professionals, and the biobank.”

Patients, “[because they act] as donors during a difficult brain metastasis neurosurgery, play a crucial role and we strongly believe that it is pivotal to empower them,” the researchers explain. GEPAC (Spanish Group of Patients with Cancer) is also involved with RENACER.

Source: Spanish National Cancer Research Centre (CNIO)

Categories : CancerTags :

In Vitro Cancer Cells Differ to Those in Body

On By ModernMedia
Photo by Drew Hays on Unsplash

A new study has shown that most cancer cells grown in vitro have little in common genetically with cancer cells in humans.

Human cancer cells grown in culture dishes have the least genetic similarity to their human sources, according to a new computer-based technique developed by researchers at John Hopkins.

According to the researchers, the finding should help shift more resources to cancer research models such as genetically engineered mice and balls of human tissue known as ‘tumouroids’ to better evaluate human cancer biology and treatments, and the genetic errors responsible for cancer growth and progress.

“It may not be a surprise to scientists that cancer cell lines are genetically inferior to other models, but we were surprised that genetically engineered mice and tumouroids performed so very well by comparison,” says Patrick Cahan, PhD, associate professor of biomedical engineering at The Johns Hopkins University and the Johns Hopkins University School of Medicine and lead investigator of the new study.

The new computer modelling technique, CancerCellNet, compares the RNA sequences of a research model with data from a cancer genome atlas to see how closely the two sets match up.

On average, genetically engineered mice and tumouroids have RNA sequences most closely aligned with the genome atlas baseline data in 4 out of every 5 tumour types they tested, including breast, lung and ovarian cancers.

This adds to evidence that cancer cell lines grown in the laboratory have less parity with their human source due to the many differences between a human cell’s natural environment and a laboratory growth environment, the researchers said. “Once you take tumours out of their natural environment, cell lines start to change,” said Prof Cahan.

Around the world, scientists depend on a range of research models to enhance their understanding of cancer and other disease biology, and to develop treatments for conditions. Of these, one of the most widely used is cell lines created by extracting cells from human tumours and growing them with various nutrients in laboratory flasks.

Other methods involve mice that have been genetically engineered to develop cancer, or implanting human tumours into mice, known as xenografting, or use tumouroids.

To investigate the accuracy of these models, scientists often transplant lab-cultured cells or cells from tumouroids or xenografts into mice and see if the cells behave as they should — that is, grow and spread, retaining the genetic hallmarks of cancer. However, the researchers contend that this process is expensive, time-consuming and scientifically challenging and so they developed a more streamlined method. The new technique is based on genetic information about cellular RNA.

“RNA is a pretty good surrogate for cell type and cell identity, which are key to determining whether lab-developed cells resemble their human counterparts,” said Prof Cahan. “RNA expression data is very standardised and available to researchers, and less subject to technical variation that can confound a study’s results.”

To start, Prof Cahan and his team had to choose a standard set of data that acted as a baseline to compare the research models. They used data from The Cancer Genome Atlas as ‘training’ data, which includes RNA expression information of hundreds of patient tumour samples, and other information on the tumour.

They also tested their CancerCellNet tool by applying it to data where the tumour type was already known, such as from the International Human Genome Sequencing Consortium.

The John Hopkins researchers combed through The Cancer Genome Atlas data to select 22 types of tumours for study, and used that data as the baseline for comparing RNA expression data from cancer cell lines, xenografts, genetically engineered mouse models and tumouroids.

Some differences observed included prostate cancer cells from a line called PC3 that started to look genetically more like bladder cancer, Prof Cahan noted. It’s also possible, he said, that originally  the cell line was simply labelled incorrectly, or else it could have in fact been derived from bladder cancer. But, from a genetic standpoint, the prostate cancer cell line was not a representative surrogate for what happens in a typical human with prostate cancer.

According to a 0-1 scoring method, cell lines had, on average, lower scoring alignment to atlas data than tumouroids and xenografts.

Prof Cahan said he and his team will be improving the reliability of CancerCellNet by adding additional RNA sequencing data.

Source: John Hopkins Medicine

Journal information: Da Peng et al, Evaluating the transcriptional fidelity of cancer models, Genome Medicine (2021). DOI: 10.1186/s13073-021-00888-w