Novel RNA interference screening technique identifies possible path for malignant glioma treatment

May 25, 2010

Researchers at the University of Massachusetts Medical School report in the journal Nature Medicine on a cellular pathway in the deadly brain cancer malignant glioma, a pathway essential to the cancer's ability to grow - and a potential target for therapy that would stop the cancer's ability to thrive.

In the paper "A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications," appearing this week as an Advanced Online Publication, UMass Medical School Professor Michael R. Green, MD, PhD, and colleagues use a genome-wide RNAi screening tool to identify a dozen genes that affect the function of a crucial protein necessary for glioma cells to grow; further research found a key pathway that appears in laboratory cultures and mouse models to be susceptible to two cancer drugs already in use for other types of cancer.

A hallmark of cancer is uncontrolled cell growth, often caused by overexpression of genes that help cells survive, or underexpression of those genes that induce normal cell death. Genes that are expressed highly in and are essential for their survival are appealing targets for drug therapy.

Green's lab has in recent years developed a clever way of scanning the genome to identify genes that appear to promote the natural process of programmed cell death called "apoptosis", or that inhibit the growth of cells; Green and colleagues used a technique called genome-wide screening—to identify novel genes that regulate the expression of a transcription factor called ATF5 in malignant glioma cells. The discovery of at least one previously unknown that appears to regulate this key transcription factor, and the subsequent determination that the sorafenib and temozolomide inhibit glioma growth point to dramatic new possibilities for potential therapeutics and are exciting advances at the frontier of cancer biology and genetic expression.

ATF5 was first identified as an important pro-survival factor by Dr. Green in 2002.

Explore further: Cancerous tumors may spread by pure chance

add to favorites email to friend print save as pdf

Related Stories

'Gateway' gene discovered for brain cancer

Feb 14, 2007

Researchers have discovered that the same genetic regulator that triggers growth of stem cells during brain development also plays a central role in the development of the lethal brain cancer malignant glioma. In experiments ...

M. D. Anderson team identifies new oncogene for brain cancer

Jul 02, 2007

An overexpressed gene found at the scene of a variety of tumors is implicated in the development of two types of malignant brain cancer in a paper by researchers at The University of Texas M. D. Anderson Cancer Center to ...

Targeted virus compels cancer cells to eat themselves

May 02, 2006

An engineered virus tracks down and infects the most common and deadly form of brain cancer and then kills tumor cells by forcing them to devour themselves, researchers at The University of Texas M. D. Anderson Cancer Center ...

Recommended for you

Cancerous tumors may spread by pure chance

28 minutes ago

The spreading of a cancerous tumor from one part of the body to another may occur through pure chance instead of key genetic mutations, a new study has shown.

Lanreotide improves survival with enteropancreatic tumors

17 hours ago

(HealthDay)—Lanreotide significantly improves survival among patients with metastatic enteropancreatic neuroendocrine tumors (grade 1 or 2), according to a study published in the July 17 issue of the New En ...

User comments : 0