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Brain Tumour

Finding keys to glioblastoma therapeutic resistance

Glioblastomas, the deadliest of all brain cancers, are notoriously resistant to drug therapy. Researchers at the University of California, San Diego School of Medicine may have found out why this is so in at least at least certain types of the killer disease.

“Our study demonstrates that the sensitivity of glioblastoma to a drug is influenced not only by the content of its DNA sequences, but also by how the DNA sequences are organized and interpreted by the cell,” said Clark Chen, MD, PhD, vice-chairman of Research and Academic Development, UC San Diego Division of Neurosurgery and the principal investigator of the study.

Chen and his team of scientists used a technique called comparative gene signature analysis to study the genetic profiles of tumor specimens collected from approximately 900 glioblastoma patients.

With this method investigators were able to say whether specific cellular processes are “turned on” or “turned off” in glioblastomas. “Based on the type of cellular processes that the cancer cells used to drive tumor growth we were able to classify glioblastomas,” said Jie Li, PhD, a member of Chen’s team.

The study showed that one of these cellular processes involving an Epidermal Growth Factor Receptor (EGFR) is suppressed in a subset of glioblastomas. This happens not because of alterations in DNA sequences or mutations but as a result of how the DNA encoding the EGFR gene is organized in the cancer cell, a form of regulation called “epigenetic.” Because in these glioblastomas the EGFR is turned off, they are insensitive to drugs designed to inhibit EGFR signaling.

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