Recreating liver tumors as organoids for faster, more accurate drug screening

February 07, 2018

[February 8, 2018] Liver cancer is one of the top causes of cancer deaths in the world, with a dearth of approved treatments. A major challenge in developing effective drugs for liver cancer is that current preclinical tumor models do not accurately replicate features of the tumor and the tumor environment in humans, causing many potential drugs to fail in clinical testing.

To more accurately mimic these features, researchers have developed models of liver tumors called patient-derived xenografts (PDX). Although these models provide a truer picture of how effective potential cancer drugs would be in humans, they are also expensive and time-consuming to create. Growing these PDX cancer cells in culture would be more cost effective for drug screening. However, so far, attempts to culture these cells fail to reflect the 3D tumor structure and the tumor environment.

Led by Dr Eliza Fong and Dr Toh Tan Boon, an interdisciplinary team of researchers at the NUS Departments of Physiology and Biomedical Engineering, the Cancer Science Institute of Singapore, the Institute of Bioengineering and Nanotechnology, A*STAR and the National Cancer Center Singapore has now devised a new method to grow PDX liver cancer cells for use in drug testing.

As described in their recent paper in the leading bioengineering journal Biomaterials, this method involves growing the cells on synthetic 3D scaffolds made of a plant-based porous hydrogel. The researchers engineered the spongy scaffolds with optimized biochemical and mechanical properties to help the liver cancer cells maintain their proper shape and function and grow as organoids.

After growing the organoids for 1 to 3 weeks, the team verified that the liver cancer cells in the organoids were alive and reproducing. Liver cancer cells usually contain specific genetic changes that are absent in normal liver cells. The researchers engineered organoids from PDX that were taken from 14 liver cancer patients. Most of the organoids retained the same key genetic changes that were in the source PDX cells. They also maintained an important feature of liver tumors called intra-tumor heterogeneity, in which distinct populations of liver cancer cells are present within the same tumor and affect its response to treatment. The presence of this feature was another advantage for drug screening that the organoids have over traditional cell culture methods, in which all cells are identical.

As a bioengineer, Dr Fong finds the success of the engineered organoids to be particularly rewarding. "This study truly epitomizes the positive synergy we can achieve in growing patient tumors outside the body by marrying advances in tissue engineering with cancer biology," she says.

Another attractive feature is the small size of the 3D scaffolds containing the organoids - a mere 100 microns. They can easily fit inside the well of a 96-well microtiter plate, a standard platform for high-throughput drug screening, which enables many drugs to be tested at the same time. Through this technology, one PDX can be used to produce tens to hundreds of such organoid-containing scaffolds. Combined with their ability to recapitulate the genetic features and heterogeneity of the original liver tumors, these tumor avatars have the potential to revolutionize the screening and development of liver cancer drugs.

In Dr Toh's words, "Having a reliable platform to grow liver cancer patient-derived cells is a major step in personalized medicine as we can now use them for increased throughput drug sensitivity testing."

Dr Hanry Yu, Professor of Physiology at NUS Medicine and Group Leader of Tissue Engineering at the Institute of Bioengineering and Nanotechnology at A*STAR, as well as the last author of the study, points out that "the spongy scaffolds developed to keep normal liver cells happy also preserve the important properties of liver cancer for drug testing. This allows patients to choose the best treatment based on the drug testing results on their own liver cancer cells."
-end-


National University of Singapore, Yong Loo Lin School of Medicine

Related Liver Cancer Articles from Brightsurf:

Eating less suppresses liver cancer due to fatty liver
Liver cancer from too much fat accumulation in the liver has been increasing in many countries including Japan.

New liver cancer research targets non-cancer cells to blunt tumor growth
'Senotherapy,' a treatment that uses small molecule drugs to target ''senescent'' cells, or those cells that no longer undergo cell division, blunts liver tumor progression in animal models according to new research from a team led by Celeste Simon, PhD, a professor of Cell and Developmental Biology in the Perelman School of Medicine at the University of Pennsylvania and scientific director of the Abramson Family Cancer Research Institute.

Liver cancer: Awareness of hepatitis D must be raised
Scientists from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the most serious consequence of chronic hepatitis: hepatocellular carcinoma.

A new treatment for liver cancer
In the latest issue of Molecular Therapy, Skoltech and MIT researchers have published a new combinatorial therapy for the treatment of liver cancer.

New study indicates exercise can help prevent liver cancer
Liver cancer is the fourth most common cause of cancer death worldwide and is growing rapidly due to the 'diabesity pandemic.' A new study reported in the Journal of Hepatology, published by Elsevier, provides strong evidence that voluntary exercise could help prevent the most common type of liver cancer, hepatocellular carcinoma, and identifies the molecular signaling pathways involved.

From obesity to liver cancer: Can we prevent the worst?
Hepatocellular carcinoma, a liver cancer linked to the presence of fat in the liver, is one of the leading causes of cancer death worldwide.

Liver cancer deaths climb by around 50% in the last decade
Liver cancer deaths have increased by around 50% in the last decade and have tripled since records began, according to the latest calculations by Cancer Research UK.

NUS researchers show potential liver cancer treatment by targeting cancer stem-like cells
NUS researchers from the Cancer Science Institute of Singapore and the N.1 Institute for Health have shown the potential use of small molecule inhibitors to treat advanced liver cancer.

Breast cancer gene a potential target for childhood liver cancer treatment
Hepatoblastoma is a rare liver cancer that mainly affects infants and young children and is associated with mutations in the β-catenin gene.

Blood transfusion during liver cancer surgery linked with higher risk of cancer recurrence and death
Receiving a blood transfusion during curative surgery for the most common type of liver cancer (hepatocellular carcinoma) is associated with a much higher risk of cancer recurrence and dying prematurely, according to new research being presented at this year's Euroanaesthesia congress.

Read More: Liver Cancer News and Liver Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.