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New Gene Sequencer is Poised to Revolutionize Mesothelioma Research

5500 SOLiD SequencerIn the U.S., mesothelioma has led to countless deaths, and currently, little can be done about it. However, the Thoracic Oncology Program at the University of California, San Francisco (UCSF) has ushered in a new era in mesothelioma research by acquiring a state-of-the-art genetic sequencing tool.

Called the 5500 SOLiD Sequencer, the device offers researchers the ability to fully sequence malignant lung cell genomes and analyze gene expression in mesothelioma tissue, often in as few as 24 hours.

The practical applications of such a device put it as the forefront of the development of potential mesothelioma treatments.

Mesothelioma is a universally fatal disease, for now

Each year, roughly 3,000 new cases of mesothelioma are diagnosed in the U.S., according to the American Cancer Society. The vast majority of cases can be attributed to asbestos exposure, even if contact with the mineral was relatively brief and occurred decades ago.

The average survival time beyond diagnosis of mesothelioma is just 15 months, the National Cancer Institute states. Annually, approximately 10,000 deaths can be attributed to asbestosis, mesothelioma and other asbestos-related conditions, according to the Environmental Working Group.

However, the origins of mesothelioma go beyond mere exposure to toxic asbestos dust. Scientists have found that cell-level changes associated with the substance appear to engender – or at least, increase the risk for – dangerous genetic mutations. It is this damage to the nucleic acids that makes mesothelioma so virulent and, following diagnosis, so fast-growing.

How is the UCSF team putting the 5500 SOLiD Sequencer to work?

The Thoracic Oncology Program has collected tissue samples from more than 160 patients with mesothelioma. These snap-frozen specimens are matched samples, meaning each individual donated both healthy lung tissue and cells afflicted with malignant mesothelioma.

Unlike other teams that hew to broad, inflexible therapeutic experimentation, the UCSF group will use the 5500 SOLiD Sequencer to develop treatments that are tailored to a mesothelioma patient’s specific genetic tumor line.

To do so, the team plans to use the new device to sequence the full genetic makeup of mesothelioma cell lines. By comparing the resulting data to normal cell samples, researchers will have the chance to locate previously undiscovered genetic mutations, potentially leading to unique treatments for the deadly disease.

With the 5500, the UCSF team members expect to be able to fully sequence even the most complex tumor cell lines in less than a week. The group expressed its enthusiasm for the innovative, individualized systems-biology approach.

Major New Mesothelioma Technology Celebrated at UCSF

From left, Vikki Friedman, Sr. Sales Representative Life Technologies Inc., Dr. Graham Scott, Director Market Development Life Technologies Inc., Mark Gardner, VP and GM Advanced Genomic Systems, Steven Kazan, Founding, Senior and Managing Principal Kazan Law, David M. Jablons, M.D. FACS Professor and Chief Thoracic Surgery UCSF Department of Surgery. Photo credit: James Hall Photography

I was honored last week to speak at an intimate reception which celebrated the inauguration of a major collaboration between global biotechnology company Life Technologies Inc. and the Thoracic Oncology Laboratory at the University of California in San Francisco. Founded in 1995 by thoracic surgeon David M. Jablons, MD and thoracic oncologist Thierry Jahan, MD, UCSF’s Thoracic Oncology Program has been at the forefront of groundbreaking laboratory research, innovative clinical trials, and compassionate, expert care for patients with mesothelioma and other thoracic malignancies.

This event marked the official dedication of 5500 Series SOLiD™ Sequencers, a machine which will drill down on the molecular underpinnings on mesothelioma, lung cancer and other thoracic malignancies.  Efforts to bring this technology to UCSF were greatly helped by the generosity of our clients, mesothelioma victim Gordon Bankhead and his wife, Emily who donated $100,000 towards the purchase of the $750,000 machine. Mr. and Mrs. Bankhead were also invited to attend the reception, but sadly could not because of his illness .

We see these kinds of philanthropic partnerships as essential to laying the foundation for innovative methods of discovery, which will be critical in helping to discover a cure for mesothelioma.

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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