Beyond birthmarks and beta blockers, to cancer prevention

Ahead of this week’s Morningside Center conference on repurposing drugs, we wanted to highlight a recent paper in NPJ Precision Oncology by dermatologist Jack Arbiser. It may represent a new chapter in the story of the beta-blocker propranolol. Several years ago, doctors in France accidentally discovered that propranolol is effective against hemangiomas: bright red birthmarks made of extra blood vessels, which appear in infancy. Hemangiomas often don’t need treatment and regress naturally, but some can lead Read more

Drying up the HIV reservoir

Wnt is one of those funky developmental signaling pathways that gets re-used over and over again, whether it’s in the early embryo, the brain or the Read more

Overcoming cardiac pacemaker "source-sink mismatch"

Instead of complication-prone electronic cardiac pacemakers, biomedical engineers at Georgia Tech and Emory envision the creation of “biological Read more

lung cancer

What cancer researchers can learn from fruit fly genetics

What can scientists studying cancer biology learn from fruit flies?

Quite a lot, it turns out.  At a time when large projects such as the Cancer Genome Atlas seek to define the changes in DNA that drive cancer formation, it is helpful to have the insight gained from other arenas, such as fruit flies, to make sense of the mountains of data.

Drosophila melanogaster has been an important model organism for genetics because the flies are easy to care for, reproduce rapidly, and have an easily manipulated genome. This NCI newsletter article describes how some investigators have used Drosophila to find genes involved in metastasis.

Emory cell biologist Ken Moberg says that he and postdoctoral fellow Melissa Gilbert crafted a Drosophila-based strategy to identify growth-regulating genes that previous researchers may have missed. Their approach allowed them to begin defining the function of a gene that is often mutated in lung cancer. The results are published online in Developmental Cell.

Part of the developing fly larva, stained with an antibody against Myopic. Groups of cells lacking Myopic, which lack green color, tend to divide more rapidly.

Moberg writes:

Many screens have been carried out in flies looking for single gene lesions that drive tissue overgrowth. But a fundamental lesson from years of cancer research is that many, and perhaps most, cancer-causing mutations also drive compensatory apoptosis, and blocking this apoptosis is absolutely required for cancer outgrowth.

We reasoned that this class of ‘conditional’ growth suppressor genes had been missed in prior screens, so we designed an approach to look for them. The basic pathways of apoptosis are fairly well conserved in flies, so it’s fairly straight forward to do this.

Explanatory note: apoptosis is basically a form of cellular suicide, which can arise when signals within the cell clash; one set of proteins says “grow, grow” and another says “brake, brake,” with deadly results.

Gilbert identified the fruit fly gene Myopic as one of these conditional growth regulators. She used a system where mutations in Myopic drive some of the cells in the fly’s developing eye to grow out more – but only when apoptosis is disabled.

Gilbert showed that Myopic is part of a group of genes in flies, making up the Hippo pathway, which regulates how large a developing organ will become. This pathway was largely defined in flies, then tested in humans, Moberg says. The functions of the genes in this pathway have been maintained so faithfully that in some cases, the human versions can substitute for the fly versions.

Myopic’s ortholog (ie different species, similar sequence and function) is the gene His-domain protein tyrosine phosphatase, or HD-PTP for short. This gene is located on part of the human genome that is deleted in more than 90 percent of both small cell and non-small cell lung cancers, and is also deleted in renal cancer cells.

How HD-PTP, when it is intact, controls the growth of cells in the human lung or kidney is not known. Gilbert and Moberg’s findings suggest that HD-PTP may function through a mechanism that is similar to Myopic’s functions in the fly.

Besides clarifying what Myopic does in the fly, their paper essentially creates a map for scientists studying HD-PTP’s involvement in lung cancer, for example, to probe and validate.

Posted on by Quinn Eastman in Cancer 1 Comment

Detecting Lung Cancer at a Higher Rate

The findings from a recent study show the risk of dying from lung cancer could be reduced by 20 percent by use of a low-dose helical computed tomography (CT) scan.  With 160,000 deaths each year related to cigarette smoking, this type of screening could save up to 32,000 lives each year.

The National Cancer Institute (NCI) launched the multicenter National Lung Screening Trial (NLST) in 2002,  led at Emory by radiologist and researcher Dr. Kay Vydareny.  This trial compared two ways of detecting lung cancer: low-dose helical (spiral) computed tomography (CT) and standard chest X-ray, for their effects on lung cancer death rates in a high-risk population.

Both chest X-rays and helical CT scans have been used as a means to find lung cancer early, but the effects of these screening techniques on lung cancer mortality rates had not been determined. Over a 20-month period, more than 53,000 current or former heavy smokers ages 55 to 74 joined NLST at 33 study sites across the United States. In November 2010, the initial findings from NLST were released. Participants who received low-dose helical CT scans had a 20 percent lower risk of dying from lung cancer than participants who received standard chest X-rays.

Read more

Posted on by Lance Skelly in Uncategorized Leave a comment

Lung cancer clinical trial shows treatment promise

Advanced non-small cell lung cancer (NSCLC) is a challenging disease to treat. More than 200,000 new cases of lung cancer are diagnosed each year, and 85 percent to 90 percent of diagnosed lung cancers fall into the non-small cell type.

A new strategy for treating NSCLC that increases the effectiveness of standard chemotherapy in patients with advanced stage disease has been found by Emory researchers. Recent advances in treatment result in improvement in patient survival noted for all stages of NSCLC.

Saresh Ramalingam, MD

Saresh Ramalingam, MD

Lead investigator Suresh Ramalingam, MD, associate professor of hematology and medical oncology at Winship Cancer Institute of Emory University, along with a consortium of academic institutions that is supported by the National Cancer Institute, published the positive results in The Journal of Clinical Oncology.

In the clinical trial, Emory scientists added a cancer-fighting compound that is used to treat a specific type of lymphoma to standard lung cancer chemotherapy, resulting in an increase in positive response rates in NSCLC patients.

The addition of vorinostat, a compound that affects the function and activity of DNA and various other proteins, to standard chemotherapy treatment of carboplatin and paclitaxel, increased positive response rates in patients from 12.5 percent to 34 percent in a clinical trial of 94 patients with metastatic non-small cell lung cancer.

Vorinostat may be affecting histones, which are spool-like proteins around which the cell’s DNA is wound. These proteins are important for cell division. We believe these molecular effects could enhance the efficacy of carboplatin and paclitaxel, respectively.

Vorinostat is part of an emerging class of anti-tumor agents that interfere with enzymes known as histone deacetylases (HDAC). Inhibiting these enzymes increases the level of acetylation, a modification of proteins in the cell. Vorinostat is sold by Merck as Zolinza and was approved by the FDA in 2006 to treat cutaneous T cell lymphoma.

Ramalingam says this exciting data will have to be further evaluated in confirmatory phase III studies before they can be adopted in routine use. However, HDAC inhibitors can now be considered among the leading targeted agents under evaluation for the treatment of non-small cell lung cancer.

Posted on by Vince Dollard in Cancer Leave a comment