Molecular reporters expose the allies of the brain tumor

December 23, 2020

Glioblastoma is the most common malignant brain tumor in adults. Roughly five in every 100,000 people develop this type of cancer each year. The diagnosis amounts to a death sentence: Even after surgical resection followed by radiation and chemotherapy, the glioblastoma will kill the patient in a few months. This is because the tumor invariably returns after treatment, and in a more aggressive form than before.

Researchers investigating glioblastoma tissue always find immune cells inside the tumor. They have therefore long suspected that these cells strengthen the tumor, instead of fighting it. A team led by Dr. Gaetano Gargiulo at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) has now supplied direct evidence of this. "We developed a new technology which allows us to visualize, on a molecular level, how the innate immune cells end up defending the tumor cells rather than body" says Gargiulo.

The researchers generated/created molecular reporters that produce fluorescence in a cell if that cell is running complex programs, such as the kind that changes the cell identity. They have published their findings in the journal Cancer Discovery. The lead authors are Matthias Jürgen Schmitt, Carlos Company, and Yuliia Dramaretska - all doctoral students in Gargiulo's Molecular Oncology Lab. The group collaborated with scientists at the Netherlands Cancer Institute, the Ludwig-Maximilians-Universität München, and the Spanish National Cancer Research Center.

Glioblastoma, previously known as glioblastoma multiforme, is a highly heterogeneous tumor. Drugs that are used successfully to treat some forms of bowel or breast cancer are powerless against glioblastoma. "This is firstly because most cancer drugs can't get across the blood-brain barrier," says Gargiulo. The blood-brain barrier is a complex set of cellular and molecular channels that regulates the access of substances to the brain tissue from circulating blood. It stops substances that don't belong in the central nervous system from entering the brain via the capillaries. This is certainly one reason why only one drug could be approved so far for chemotherapy in glioblastoma patients and it eventually stops working pretty soon.

A basis for developing new medicines

Secondly, not all cancer cells are alike. The cells that give rise to glioblastoma are divided into multiple molecular subtypes. The composition changes over time. This is especially true with a recurrence - when a tumor returns after treatment. In these cases, the cells frequently transition to the most aggressive of the subtypes, which is deadlier than the others. "A better understanding of the glioblastoma subtype identities, and of what triggers their changes, could be a guide for developing new and more effective therapies," says Matthias Schmitt.

This requires researchers to have an accurate understanding of the tumor's biology - how it regulates its growth and how it interacts with nearby cells. Gargiulo and his team have now found the tool that allows them to comprehend these cellular processes. "Within the tumor cells' genome, we've identified the regulators that program each subtype signature," says Yuliia Dramaretska. "We then turned these short DNA segments into molecular reporters that fluoresce when the cells change." They also show what triggered the change - e.g., immune cells, drugs, or ionizing radiation.

A versatile technology

"The molecular reporters can now help us work out how to stop the immune cells from making the tumor cells more aggressive," says Gargiulo, explaining the future research plans. "Perhaps we can also encourage them to recruit other immune cells that will help them fight the tumor."

The technology has already been patented, and the plan is to set up a spin-off that will further develop it. "It's not only useful with glioblastoma," says Carlos Company. "It is potentially applicable to many other biological systems." One very contemporary use that Gargiulo mentions is for research into the COVID-19. The MDC scientists plan to use it to develop tests that show, at a very early stage, whether the virus is attacking the lung tissue. They could investigate drug combinations to see whether these stop the pathogen from replicating in the cells and mount an anti-viral response. The method could also provide insights into how and why drugs work against COVID-19.
-end-


Max Delbrück Center for Molecular Medicine in the Helmholtz Association

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and 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.