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International Mesothelioma Group 2012 Young Investigator Award Recipient Yuen Yee Cheng


In celebration of the meeting of the International Mesothelioma Interest Group, or iMig 2012, we at Kazan, McClain, Satterley, Lyons, Greenwood & Oberman funded this year’s Young Investigator Awards, as we have done at each meeting since 2008. This is the second in a series discussing the promising work of one of the recipients.

Australia was once home to one of the world’s most thriving asbestos industries, which left behind a dubious legacy of health problems. Fortunately, a generation of scientists decided to respond to this legacy by establishing the Asbestos Diseases Research Institute (ADRI), located at the University of Sydney.

At iMig 2012, we had the pleasure of meeting Dr. Yuen Yee Cheng, who was happy to discuss her work on epigenetics and the suppression of malignant pleural mesothelioma (MPM) tumors.

Silencing the disease

Cancer is a complex condition that is influenced by a wide number of variables, including lifestyle choices, genetics and pollution. When it comes to MPM, the main driving factor in the development of the disease is a history of asbestos exposure, which can cause pathological changes in the mesothelial cells of the lungs.

Healthy mesothelial cells contain an active gene known as ZIC1, which plays an important role in suppressing behavior that could lead to the development of tumors. Past studies have shown in gastric and colorectal cancer cells, ZIC1 was silenced. In order to determine if the same was true in MPM, Cheng and her team conducted a study that looked at cell and tumor samples.

Results showed that the activity of ZIC1 was hampered in 16 of 24 MPM tumor samples, leading to the production of microRNAs (a type of chemical messenger within a cell) that are associated with disease activity. However, stimulating the expression of ZIC1 reduced the levels of these abnormal microRNAs, which interfered with the tumor growth.

This is an important observation because it may inspire researchers to take a new approach toward treating MPM. This disease is not going away any time soon. In fact, the Environmental Working Group predicts that we may even see more cases of it popping up in years to come.

Thankfully, scientists at places like ADRI are up to the task of solving these problems – and we are happy to support their work.

“My ultimate aim is to find a cure for mesothelioma,” Cheng told us. “I would like to thank the ADRI and the Asbestos Diseases Foundation of Australia for their support. And I would sincerely like to thank the professional law corporation Kazan, McClain, Satterley, Lyons, Greenwood & Oberman for supporting the Young Investigator Award.”

Related posts:

International Mesothelioma Interest Group Young Investigator Award Recipient Licun Wu

International Mesothelioma Interest Group 2012 Young Investigator Award Recipient Karin Schelch

 

International Mesothelioma Interest Group 2012 Young Investigator Award Recipient Karin Schelch

In celebration of the meeting of the International Mesothelioma Interest Group, or iMig 2012, we at Kazan, McClain, Satterley & Greenwood funded this year’s Young Investigator Awards, as we have done at each meeting since 2008. This is the first in a series discussing the promising work of one of the recipients.

If there is one thing that defines a researcher, it is a never-ending desire to improve upon science’s current body of knowledge. When it comes to the search for a cure for malignant pleural mesothelioma (MPM), this drive usually means good news for patients.

At iMig 2012, we met Karin Schelch, a PhD candidate in molecular biology, who was kind enough to talk to us on video about her team’s research on fibroblast growth factors (FGF) and fibroblast growth factor receptors (FGFR). Both sets of these proteins may serve as targets for MPM treatments.

Defining the roles of the proteins in MPM

According to Schelch, FGF is important for the growth and survival of cells. However, it can also drive the development of several types of malignancies.

Despite this knowledge, the specific role of FGF in MPM had not always been entirely clear. This makes FGF and FGFR important topics for research because a better understanding of their biology can, in turn, lead to a better understanding of how to tackle mesothelioma.

In the laboratory, Schelch and her team conducted several experiments that included MPM cell models, normal mesothelial cells and human tissue samples. Specifically, the researchers were looking at what cells made what proteins.

Ultimately, they found that MPM cells and tumorous tissues have three abnormally active genes: FGFR1, FGF2 and FGF18. Through different experiments, the scientists discovered that stimulating the cells with FGF2 made them more invasive, and that blocking the actions of FGFR1 made the spread and survival of cancer cells more difficult.

“Our data show that blocking the fibroblast growth factors could be a new and more efficient option for mesothelioma treatment,” Schelch told us.

Furthermore, one experiment revealed that diseased cells that are resistant to cisplatin, a standard medication for MPM, are also more sensitive to FGFR1 inhibition. This is good news, considering that Schelch and her team theorize that blockage of FGFR1 could work well in combination with chemotherapy and radiation treatments.

These results were so exciting that the team presented this study at iMig 2012. And on behalf of MPM patients everywhere, we are happy to support work like this.

Related posts:

International Mesothelioma Interest Group Young Investigator Award Recipient Licun Wu

International Mesothelioma Group 2012 Young Investigator Award Recipient Yuen Yee Cheng

Latest Breakthrough in Experimental Mesothelioma Treatment: Antibody-Drug Conjugates

cellsRoughly a century ago, German immunologist Paul Ehrlich was staining cell cultures when he had a radical thought. He wondered, if staining techniques could target a single strain of bacteria, then what’s to stop scientists from eventually developing a “magic bullet” treatment for every disease, one that is highly targeted and has few or no side effects? As a chemotherapy pioneer, Ehrlich even broadened this notion to include cancers.

Though he never saw anything like it in his lifetime, today, Ehrlich’s dream may have been finally realized. That’s because scientists are currently testing an experimental form of cancer treatment, called antibody-drug conjugates (ADCs).

This unusual form of cancer treatment combines homing ability of human antibodies with the cancer-killing power of chemo drugs or cytotoxins. Such innovations may soon be the “magic bullet” for treating malignant pleural mesothelioma (MPM) and other severe diseases.

A new direction in mesothelioma research

ADCs have gotten quite a bit of attention lately, and for good reason. Clinical studies have shown that a such drugs can have remarkable tumor-shrinking properties, while causing fewer and less severe side effects than traditional chemotherapies.

In fact, ADCs are such a hot topic right now that they recently appeared as the subject of a New York Times article on cutting-edge breast cancer therapies.

Stephen Evans-Freke, a general partner of a pharma investment firm, told the newspaper that preliminary ADC trial results make them look exceedingly promising – for patients and pharmaceutical manufacturers alike.

“I don’t think there is a major pharma or a mid-sized pharma with interest in cancer that doesn’t have [an ADC] program or isn’t scrambling to put one together,” he explained.

So what are ADCs and how do they work?

Two halves, linked

At its simplest, an ADC consists of three things. First, a human antibody (or immune protein) that identifies a specific form of cancer. This is then attached to a chemotherapy agent or cytotoxin. The third bit, and a critical one at that, is the small molecule that links the first two.

When introduced into the bloodstream, ADCs do not attack indiscriminately, they way traditional chemo agents do. Instead, their targeted antibodies allow them to seek out tumors and deliver the cytotoxins, which then kill malignant cells.

According to the Society of Toxicology, this unique construction makes ADCs something of a molecular guided missile, increasing the maximum tolerated dose and decreasing the minimum effective dose.

And their targeted nature gives ADCs unmatched potential. In an article for Genetic Engineering and Biotechnology News (GEBN), pharma developer ImmunoGen estimated that ADCs are often between 1,000 and 10,000 as potent as typical chemo drugs.

All these characteristics could make these novel formulations a welcome new weapon in the fight against mesothelioma.

A not-so-novel idea, reborn

While ADCs may sound brand-new, they have been in the works since the 1980s. However, according to GEBN, they suffered a decline in popularity that lasted nearly 25 years. It only ended around 2005, when clinical trials began revealing the wonders that such drugs can accomplish.

Today, dozens of ADCs are in development, at least one for every major type of cancer – MPM included. In 2011, researchers from Bayer Pharmaceuticals registered BAY 94-9343, an ADC that targets mesothelin, a protein that is overproduced in all forms of mesothelioma.

Using a cytotoxin called DM4, this drug binds to and kills only cells that produce mesothelin – and the more mesothelin a malignant cell creates, the more likely it is to absorb BAY 94-9343 and die.

At Kazan, McClain, Lyons, Greenwood and Harley, we know that it’s treatment developments like this that give MPM patients continued hope of living a longer, fuller life.

Related articles:

Mesothelioma Clinical Trials: What They Are, How They Work, How to Participate

5 Doctors Receive Mesothelioma Research Grant Awards

New Theories for Gene Therapy Offers Hope to Malignant Mesothelioma Victims

University of Pennsylvania School of Medicine

It has been theorized that Malignant Mesothelioma may be a good target for gene therapy because the thin mesothelial layer offers a large surface area for gene transfer, with the pleural space easily accessible for biopsy. A recent article in Current Treatment Options in Oncology by University of Pennsylvania researchers described novel approaches to gene therapy offering new hope to those suffering from this dreaded disease.

How Mesothelioma Grows

In their review of gene therapy clinical trials, the authors reported some ” limited evidence of efficacy ” for this treatment. Mesothelioma occurs when proteins allow cells to grow in an uncontrolled manner. A specific protein called mesothelin was found by researchers looking for differential expression of proteins between normal cells and mesothelioma cells. The increased presence of mesothelin on certain cells is thought to enable their growth, leading to mesothelioma.

Promising New Approaches

Previous laboratory research has shown that certain immune system cells, called T cells, can kill tumor cells that express mesothelin. In addition, both animals and human studies have shown that antibodies directed against mesothelin protein can shrink tumors. As a result, much of the mesothelioma research currently underway is focused on developing therapies that can directly block mesothelin function. One especially promising new area in gene therapy is the use of lentiviral or retroviral vectors to “transduce T-cells with modified T-cell receptors engineered to attack specific tumor antigens”. This approach has shown some success in treating other cancers.

Conclusions

The authors conclude “At this point in time, gene therapy for mesothelioma remains experimental and limited to a few referral centers. However, the practicing clinician can participate in moving this approach forward by not taking a nihilistic approach to MPM, but by discussing option of participating in clinical trials with his patients”.

For more information contact the University of Pennsylvania Gene Therapy Program.

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