‘Genetic doppelgangers:’ Emory research provides insight into two neurological puzzles

An international team led by Emory scientists has gained insight into the pathological mechanisms behind two devastating neurodegenerative diseases. The scientists compared the most common inherited form of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) with a rarer disease called spinocerebellar ataxia type 36 (SCA 36). Both of the diseases are caused by abnormally expanded and strikingly similar DNA repeats. However, ALS progresses quickly, typically killing patients within a year or two, while the disease Read more

Emory launches study on COVID-19 immune responses

Emory University researchers are taking part in a multi-site study across the United States to track the immune responses of people hospitalized with COVID-19 that will help inform how the disease progresses and potentially identify new ways to treat it.  The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The study – called Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) – launched Friday. Read more

Marcus Lab researchers make key cancer discovery

A new discovery by Emory researchers in certain lung cancer patients could help improve patient outcomes before the cancer metastasizes. The researchers in the renowned Marcus Laboratory identified that highly invasive leader cells have a specific cluster of mutations that are also found in non-small cell lung cancer patients. Leader cells play a dominant role in tumor progression, and the researchers discovered that patients with the mutations experienced poorer survival rates. The findings mark the first Read more

cancer stem cells

Hippo dances with hormones

Although fruit flies don’t develop cancer, cancer and stem cell researchers have been learning a great deal from fruit flies – in particular, mutant flies with overgrown organs that resemble hippopotamuses.

A fly gene called Hippo and its relatives in mammals normally block cell proliferation and limit organ size. When flies have mutations in Hippo or other genes (together dubbed the Hippo pathway), the resulting overgrowth distorts their tissues into hippopotamus-like bulges. See Figure 3 of this review for an example. In humans, the Hippo pathway is involved in forming embryonic stem cells, suppressing cancerous growth, and also in regenerative growth and wound healing..

Working with flies, researchers at Emory have found that the abnormal growth induced by Hippo pathway disruption depends on genes involved in responding to the steroid hormone ecdysone.

Their results were published Thursday, July 2 in Developmental Cell.

“Ecdysone is, to some degree, the fly version of estrogen,” says senior author Ken Moberg, PhD, associate professor of cell biology at Emory University School of Medicine.

Ecdysone

In fly larvae, ecdysone triggers metamorphosis, in which adult structures such as wings and eyes emerge from small compartments called imaginal discs.. Ecdysone has a chemical structure like that of estrogen, testosterone and other steroid hormones found in humans. Ecdysone is not sex-specific, but it acts with the same mechanism as other steroid hormones, diffusing into cells and binding proteins that bind DNA and regulate gene activity. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Strategies to target cancer stem cells

A story in last Friday’s New York Times highlights research on “cancer stem cells”: a fraction of cells in a tumor that are especially resistant to chemotherapy and resemble the body’s non-cancerous stem cells in their ability to renew themselves.

The story describes work by a team at the Broad Institute, who reported in the journal Cell that they had identified compounds that specifically kill cancer stem cells. The hope is that compounds such as these could be combined with conventional treatments to more effectively eliminate cancers.

However, scientists disagree on whether the phenomenon of cancer stem cells extends to different kinds of cancer and what is the best way to target them. Previously not much was known about how to attack these cells.

Work at Emory’s Winship Cancer Institute has been tracking how some biomarkers in cancer cells resemble or differ from those found in stem cells. These markers may help researchers home in on the cancer stem cells.

 

Anticancer therapy must target more than one type of cell. TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor

If "cancer stem cells" play the critical roles some scientists think they do, anticancer therapy must target more than one type of cell. In this figure from Van Meir + Hadjipanayis' review, TIC means tumor initiating cell, DTC means differentiated tumor cell, and CPG means cancer progenitor cells.Â

 

 

In a recent review, Emory brain cancer specialists Erwin Van Meir and Costas Hadjipanayis write:

The “cancer stem cell” hypothesis has invigorated the neuro-oncology field with a breath of fresh thinking that may end up shaking the foundation of old dogmas, such as the widely held belief that glioblastoma tumors are incurable because of infiltrative disease. If the infiltrated cells are in fact differentiated tumor cells, their dissemination beyond the surgical boundary may not be the primary cause of tumor recurrence.

Van Meir, the editor of a new book on brain cancer, adds this comment:

Clearly a lot more work needs to be done to understand the precise cause of glioblastoma recurrence after surgery and chemotherapy and how to prevent it.  The possibility of developing therapeutics that can specifically target the brain cancer stem cells is an exciting new development but will have to proceed with caution to spare normal stem cells in the brain. Developing new imaging tools that can track cancer stem cells in the brain of treated patients is also an important objective and some of the Emory investigators are evaluating the use of nanoparticles to this purpose.

A new faculty member at Winship, Tracy-Ann Read, recently published her research on a molecule that could be used to identify “tumor-propagating cells” in medulloblastoma, a form of brain cancer. She says:

Although cancer stem cells have been identified in many different types of cancer, it is becoming increasingly clear that the properties of these cells may vary greatly among the different tumor types. It is unlikely that one  therapeutic agent will be able to target the cancer stem cells in for example all types brain tumors. Hence  much work still needs to be done in terms of analyzing the properties of these cells in each tumor type and identifying the genes that are responsible for their unique ability to propagate the tumors. 

Winship’s director Brian Leyland-Jones has also reported at the San Antonio Breast Cancer Symposium that molecules that distinguish a hard-to-treat form of breast cancer resemble those that maintain stem cells.

Nice round-up from Nature’s stem cell blog editor Monya Baker

Posted on by Quinn Eastman in Cancer Leave a comment