Cancerous tumors have complex structures that exhibit dynamic microenvironments and intricate signalling networks. Thanks to cellular mutations, accurately predicting how they react to specific drugs and treatment protocols is often a herculean task.
While animal testing can help us in the initial testing stages, it is not 100% perfect at replicating the characteristics of a tumor microenvironment in the human body. For obvious reasons, there are significant limitations to conducting early-phase testing and experiments on human patients.
Organoids might offer us a way out of this dilemma. We have already covered these lab-grown tissue cultures in several other articles focusing on vaccine development and cancer research, particularly in dealing with highly lethal forms of the disease.
In this context, two recent studies involving organoids caught my eye. They both deal with cancers that are tough to crack, for myriad reasons – glioblastoma or brain tumors, and pancreatic cancer. The breakthroughs are interesting because they show us a glimpse of the future of cancer research.
A Quick Look at Organoids
An organoid is a miniature replica of organ tissues, grown in labs from stem cells or organ-specific progenitor cells. They are typically grown in specialized culture mediums in vitro (outside a living organism).
Over time, the stem cells grow into tiny three-dimensional tissue cultures that have the same structure and function as real organs. Scientists have managed to create organoids of the lungs, kidneys, liver, and even the human brain.
The technology offers promise in multiple areas of medical research. They could help us develop transplantable organs that are a perfect match for recipients, reducing the risk of organ rejection post-surgery.
Organoids can also be used to study the inner workings of complex organs and for the testing of new drugs. Researchers are also using them to study how diseases affect specific organs, a process called disease modelling.
Disease modelling is especially relevant in cancer research, as it helps scientists understand better how tumors develop, progress, and respond to treatments. Organoids allow them to do this in a highly controlled and infinitely replicable way.
Brain Tumor Organoids Can Help Forecast Treatment Response
Apart from growing miniature copies of healthy organs, the technology can also be used to create replicas of tumors. In a study published in Cell Stem Cell, a team of researchers from the University of Pennsylvania proved that organoids can help us model how individual patients respond to treatment.
In the study, researchers from the Perelman School of Medicine created organoids of glioblastomas using mutated stem cells from six brain cancer patients undergoing clinical trials for an experimental CAR T cell therapy.
Both the patients and their organoids were subjected to the treatment at the same time. At the end of the treatment, tumor size and toxicity levels were measured. The organoids showed the same response as their donor patients in all tested metrics.
This could be a game changer in our fight against glioblastoma, an often lethal form of brain cancer that only leaves patients less than a year to live after diagnosis. The cancer can take many forms and affect various parts and tissues of the brain, making it hard to predict how a patient will respond to drugs.
One option is to grow the patient’s cancer cells in the lab for testing. However, this is a time-consuming process that can take several months. Meanwhile, it only takes a few weeks to create an organoid from scratch.
Given the aggressive nature of glioblastomas, surgery is generally prescribed as the first line of treatment, with treatments like CAR T acting as a follow-up. Tumor organoids for testing purposes can slot nicely into this schedule.
While the patient takes a few weeks to recuperate from the surgery, doctors can culture an organoid and test the follow-up drug on it to see if it can deliver the required results. The tests would allow doctors to decide the best drug to use, along with safe dosage, for each patient separately.
Pancreatic Tumor Organoids Help Demystify Cancer Diversity
Like the brain, the pancreas is another organ where cancers tend to have a very high mortality risk. The causes are also quite similar, with tumor diversity and a tendency to react in multiple ways to the same treatment, depending on the location of the cancer cell clusters.
Researchers at the Technical University of Munich (TUM) have managed to grow tumor organoids from pancreatic cancer cells for the first time ever. Using AI and machine learning, the team was able to classify the organoids into various phenotypes.
Prior to this, pancreatic tumor nodules were broadly classified into two main types – epithelial and mesenchymal. Thanks to the organoids, we now have multiple subtypes within these two families, each with unique properties and reactions toward therapies.
For example, one phenotype had a distinct star-like appearance and was found to be highly resistant to existing chemotherapy drugs. However, further analysis revealed a vulnerability to radiation. Such breakthroughs open up exciting new possibilities in terms of personalized therapies.
Pancreatic cancers do not manifest symptoms until they reach relatively advanced stages. The presence of multiple phenotypes and genotypes can make the disease even harder to treat. Treatment plans involving a single drug will have limited odds of success as some phenotypes could be highly resistant.
The TUM research study indicates a need for a fresh approach that involves new drugs that can reduce the diversity of tumor nodules through targeted suppression of specific phenotypes. Having fewer active phenotypes could increase the chance of successfully treating the cancer.
With over 500,000 cases reported and a 5-year survival rate of just 13%, pancreatic cancer is the seventh leading cause of cancer-related deaths across the world. Meanwhile, glioblastoma is the most common type of brain tumor in adults, with an even bleaker 5-year survival rate of 6.9%.
Tumor organoids have the potential to drastically improve those odds by offering us deeper access to hitherto unreachable sections of deadly tumors. We can expect further breakthroughs in this space in the years to come.
