New research published in cancer discovery identifies new drug target for glioblastoma

August 21, 2019

Wednesday, August 21, 2019, CLEVELAND: A new international study co-led by Cleveland Clinic has identified a new drug target for treating glioblastoma. This target is part of a never-before defined cellular pathway found to contribute to the spread and proliferation of a dangerous subset of cancer cells, called glioma stem cells.

While previous research has shown that a protein called FGF2 (fibroblast growth factor 2), when activated ("turned on"), contributes to glioma stem cell self-renewal and tumor growth, it was not understood how. This study, co-led by Justin Lathia, Ph.D., Cleveland Clinic Lerner Research Institute, identifies FGF2 as an important intermediary in a multi-step, pro-cancer signaling loop and suggests that "turning off" FGF2 may halt the growth and spread of glioblastoma.

Published in the August 21 issue of Cancer Discovery, this study is the first to identify FGF2 as a novel druggable target for glioblastoma, the most common primary malignant brain tumor. With standard treatment, the median survival for adults with glioblastoma is only between 11 and 15 months, and recurrence is very common. New therapies are greatly needed.

Extracellular matrix (ECM) is a network of molecules that--like brick and mortar--help to hold and anchor nearby cells together. The research team found that a protein called ADAMDEC1 (a disintegrin and metalloproteinase domain-like protein decysin 1), which is secreted by glioma stem cells, breaks down ECM. In its absence, cancer cells are able to access key nutrients for their growth that otherwise would not be available.

One of these nutrients is FGF2. The team of researchers showed that ADAMDEC1 activates FGF2, which is found within the tumor microenvironment. Like a lock and key, the "turned on" FGF2 selectively binds to and activates a receptor found on the surface of glioma stem cells, called FGFR1 (FGF receptor 1).

FGFR1, mediated through a few additional signaling cascades, plays two important roles in driving glioblastoma. It helps to mediate the hallmark pro-cancer characteristics of glioma stem cells, including their ability to self-renew and spread. Additionally, FGFR1 signaling ultimately induces the expression of ADAMDEC1, which sends this whole cellular feedback loop into motion again.

"These findings are exciting because they put forth a new paradigm for glioma stem cell regulation," said Dr. Lathia. "This pathway shows that glioma stem cells' ability to access key nutrients in their surrounding microenvironment, by way of ADAMDEC1, is integral for their maintenance and spread. Finding a way to interrupt this feedback loop will be important for treating glioblastoma."

While additional research is necessary, this study suggests that therapeutically targeting FGF2 may be the key to interrupting this cancer-driving loop.
-end-
Dr. Lathia is co-director of Cleveland Clinic Center for Excellence in Brain Tumor Research and Therapeutic Development, which brings together traditional lab scientists with front-line physicians to advance care for glioblastoma patients.

Dr. Lathia's collaborators on this study include co-leader, Dr. Florian Siebzehnrubl from the European Cancer Stem Cell Research Institute in Cardiff, Wales; Drs. Karl Holmberg and Karin Forsberg-Nilsson from Uppsala University, Sweden; Dr. Giorgio Colombo from the University of Pavia, Italy; Dr. Giulia Taraboletti from Istituto di Ricerche Farmacologiche, Italy; and Dr. Thomas McIntyre from Lerner Research Institute.

Funding from the Lisa Dean Moseley Foundation to Dr. Lathia helped support this study.

Cleveland Clinic

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science 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.