Best of iMig 2014: Day 2

Dr. Hassan Receives Wagner Award***The Best of iMig 2014 updates were created by iMig and distributed to conference attendees during iMig 2014. The following is a verbatim re-post of those updates.***

2014 Wagner Medalist Announced

Dr. Raffit Hassan discusses immunologic interventions in mesothelioma
Click here to watch Dr. Raffit Hassan

The 2014 winner of the Wagner Medal was Raffit Hassan. Dr. Hassan was trained in Kashmir and the United States and is currently Head, Thoracic and Solid Tumor Immunotherapy Section, Center for Cancer Research at the National Cancer Institute.  Dr. Hassan has played pivotal role in validating the tumor differentiation antigen mesothelin as a target for cancer therapy and development of mesothelin targeted immunotherapy. This work has laid the foundation for several mesothelin directed agents that he is evaluating in the clinic for treatment of mesothelioma, lung and pancreatic cancer. Dr. Hassan has published extensively in pleural mesothelioma and was recently given the Pioneer Award by the Mesothelioma Foundation.  His award lecture was focused on mesothelin-targeted therapies for the treatment of mesothelioma.

Asbestos Exposure – A Long and Troubling History

Asbestos Blues: A History of Asbestos Mining in South Africa – Jock McCulloch
Australia and South Africa are the only countries to have mined crocidolite or blue asbestos. Crocidolite was mined in the Northern Cape for one hundred years and at Wittenoom in Western Australia from 1944 until 1966. Mining has left a pandemic of asbestos disease in the Northern Cape and although production levels were modest, Wittenoom has become the site of Australia’s worst occupational health disaster. The mines of the Northern Cape also supplied the first conclusive evidence linking asbestos to mesothelioma, but discovery had no impact on the global consumption of asbestos.

Corruption is a serious problem in communities burdened by asbestos-related disease and this has justifiably bred profound mistrust of outsiders involved in asbestos compensation, research, or litigation. This corruption has involved both suppression and destruction of knowledge and this has been one of the most effective strategies employed by the asbestos industry.  The history of suppression of information documenting the dangers of asbestos exposure dates back to the 1930’s when the work of George Slade demonstrating the health effects of asbestos exposure in miners was suppressed and ultimately destroyed.  These actions contributed to the absence of any regulation at all of asbestos mining in South Africa until 1955.  In the United States, the asbestos industry actually paid researchers to claim that asbestos was not significantly associated with mesothelioma.  Corruption of science slows regulatory legislation and limits the success of litigation aimed at compensating victims.

Occasional Exposure to Asbestos: What is the Risk? – Sjaak Burgers
The question “What is the risk of occasional asbestos exposure?” has a scientific, a political and a social answer, which are all interrelated.

Data from populations with a low, occasional asbestos exposure is scarce. A search in Western Australia uncovered asbestos exposure, sufficient to cause mesothelioma in almost all cases. Whether the risk for mesothelioma and lung cancer increases linearly or has a particular threshold is still not completely clear, but the weight of evidence supports the view that even occasional asbestos exposure is related to increased risk for mesothelioma and lung cancer.  Observations supporting the view that even minimal asbestos exposure carries significant risk have provided the basis for political discussions on reimbursement for asbestos victims. These data have been used by the World Health Organization and national policy makers to set the Maximal Tolerated Risk and the Negligible Risk Level for asbestos exposure in the working environment and at home.

In the Netherlands, the same risk estimates are part of the guideline “Occasional Asbestos Exposure”. This guideline covers the laws and regulations on asbestos, and focuses on reliable quantification of the exposition, and uses the risk estimates to educate the victims about the health risks. It has proven to be helpful to ease the panic that usually accompanies the discovery of asbestos in the neighborhood.

New Molecules and New Therapies – Advancing Mesothelioma Care

Keynote, Dean Fennell presents on treatment developments for mesothelioma
Click here to watch Dean Fennell

Paul Bass summarizes evidence from studies showing specific targeting of cancer stem called by defactinib, a novel inhibitor of FAK
Click here to watch Paul Baas

Role of Focal Adhesion Kinase (FAK) Inhibition in Mesothelioma – Ravi Salfia
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in signal transduction pathways that are initiated at sites of integrin-mediated cell adhesions and by growth factor receptors. It is a key regulator of survival, proliferation, migration and invasion, all of which are all involved in the development and progression of cancer.  FAK has also been implicated in the phosphorylation of several focal adhesion associated proteins, including paxillin.  Overexpression and/or increased activity of FAK is common in a wide variety of human cancers and a large and growing body of literature has provided strong evidence that FAK has important roles in tumor formation and metastasis.

Inhibition or modulation of FAK would appear to be a potential way to treat multiple cancers, including mesothelioma. However, since FAK is a strong mediator of survival signaling, tumor cells with high levels of FAK could be more resistant against classic anti-cancer therapy. There are now multiple agents that specifically target FAK and inhibit this kinase.  Studies of FAK inhibitors in vitro and in animal models of different cancers have shown that these agents effectively decrease tumor growth, decrease invasion and metastasis, and inhibit pancreatic tumor microenvironment components, such as tumor associated fibroblasts and macrophages.  FAK inhibition also promotes apoptosis and modulates the activity of nuclear factor E2-related factor 2 (Nrf2).  The effects of FAK inhibition on Nrf2 activity may be particularly important since the Nrf2 signal pathway may function to protect cancer cells from against drug-induced cell death. Clinical trials with FAK inhibitors in patients with mesothelioma are now in progress.

Raphael Bueno presents the design of the phase II study of the new FAK inhibitor, defactinib for the treatment of patients with mesothelioma
Click here to watch Raphael Bueno

Establishing Tissue Banks to Support Mesothelioma Research

MESOBANK: A Clinicobiological Database for Epidemiological and Translational Research for Mesothelioma – Françoise Galateau-Sallé
The French Ministry of Health and the National Cancer Institute have funded the Clinico-biological database for epidemiological and translational research since 2011. The goal of this project was to collect structured data on follow-up and outcomes in order to structure a collection of samples of high quality for use in basic and translational research, to develop inter-institutional systems and to establish quality management policies.

The collaborative effort of the French Multicentic National Register network MESONAT and of the Center of Excellence MESOPATH made it possible to extend these efforts to mesothelioma by the creation of MESOBANK, a virtual and exhaustive repository of national data and samples pertaining to mesothelioma. The MESOBANK database was interconnected with that of the National Referent Center on pleural malignant mesothelioma and rare peritoneal tumors, supported by the French National Cancer Institute and is was also was closely networked with the National Program for Monitoring of Mesothelioma, the French MESONAT network and with the International Excellence Center.

The MESOBANK has gathered 7,725 mesothelioma samples (with >10,000 paraffin embedded blocks and 1,489 frozen tissue samples) from patients with certified diagnoses of mesothelioma. Assessment of these tissues has included systematic analysis of 10 immunohistochemical markers, and p16 deletion by FISH, allowing studies of sensitivity of markers for the diagnosis and prognosis of mesothelioma with a high statistical power. MESOBANK can provide support for new basic genomic and pharmacogenomic research programs to foster a better understanding of the molecular basis of mesothelioma and improved early detection and management of this disease.

MesobanK UK – An International Bioresource of Mesothelioma Tissue – Robert Rintoul
Availability of quality assured, fully annotated mesothelioma tissue collected to rigorous standard operating procedures (SOPs) to facilitate basic and translational research, is very limited. MesobanK in the United Kingdom (UK) was funded by the British Lung Foundation and Mick Knighton Mesothelioma Research Fund to provide researchers with access to a wide range of samples from patients with this disease.

The overall objectives of MesobanK are to:

  • Construct a tissue microarray (TMA) from 1000 cases of mesothelioma linked to a clinical data set.
  • Collect 300 cases of fresh mesothelioma tissue, whole blood, serum, and plasma linked to a clinical data set with follow up data from the National Cancer Registration Service.
  • Develop 20 new fully annotated mesothelioma cell lines.

MesobanK abides by all relevant United Kingdom and European Union legislation regarding the collection of tissue and data. The project is overseen by a Steering Committee and an independent Scientific Advisory Board reviews applications for samples, which are prioritized for access based solely on scientific merit.

To date, 500 of the 1000 mesothelioma case designated cases for TMA have been acquired from UK pathology departments and the TMA construction is underway. Several new cell lines are also being characterized. Quality assurance and control are being undertaken to ensure suitability for research use.

MesobanK will also act as a repository for samples collected within clinical trials.

Dr. L Mutti speaks on novel strategies and critical biomarkers for mesothelioma
Click here to watch Dr. Mutti 

To learn more about iMig 2014, read Best of iMig 2014: Day 1 and Best of iMig 2014: Day 3.

“Best of iMig 2014” has been supported by the unrestricted sponsorship of Versastem, Inc.

***The Best of iMig 2014 updates were created by iMig and distributed to conference attendees during iMig 2014. The following is a verbatim re-post of those updates.***

The Meso Foundation Congratulates Dr. Hassan for Prestigious Award

Hassan_WagnerAwardThe Mesothelioma Applied Research Foundation congratulates Dr. Raffit Hassan of the National Cancer Institute (NCI) on receiving the prestigious Wagner Award at this year’s International Mesothelioma Interest Group’s (iMig) meeting.

Raffit Hassan, MD, is an Investigator and Chief of the Solid Tumor Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute. Dr. Hassan is a medical oncologist whose laboratory and clinical research is focused on developing novel therapies for the treatment of mesothelioma. His work and collaborations have shown that mesothelin, a tumor antigen that was discovered at the NCI, is a useful target for tumor-specific therapy of malignant mesothelioma. His group is presently conducting clinical trials of three different agents targeting mesothelin namely, SS1P, an anti-mesothelin immunotoxin, MORAb-009, a chimeric anti-mesothelin monoclonal antibody, and CRS-207, a mesothelin tumor vaccine.

Dr. Hassan served on the Meso Foundation’s Science Advisory Board for nearly a decade and for three years was the chair of the board. The Meso Foundation is grateful for all of his contributions to the field of mesothelioma.

The Wagner Award is named after J. Christopher Wagner, who was a leader in the field of mesothelioma by making major contributions to the understanding of mesothelioma, its cause and the goals for prevention. Wagner was the first to establish the connection between mesothelioma and asbestos.The Wagner award is presented every two years to an individual who has made major original contributions to the understanding of mesothelioma, either in basic or applied research.

Previous recipients include Drs. Joseph Testa, Stephen Albelda, Brooke Mossman, Harvey Pass, Bruce Robinson, and Marie-Claude Jaurand.

This year’s award was presented to Dr. Hassan by Dr. Steven Mutsaers.

Now Available: Watch the Philadelphia Regional Mesothelioma Conference Online

Philadelphia ConferenceThe content from the Meso Foundation’s regional conference, presented as a collaboration between the Mesothelioma Applied Research Foundation and Penn’s Abramson Cancer Center, held in Philadelphia on September 26, 2014, is now available for viewing online on the Abramson Cancer Center website.

The conference featured area experts in the field of mesothelioma.

All sessions are now available online at OncoLink.org/Conference/Mesothelioma.

The conference was co-chaired by Mary Hesdorffer, CRNP, of the Meso Foundation, and Joseph Friedberg, MD, and Daniel Sterman, MD, of the Penn’s Mesothelioma and Pleural Program.

Among topics of discussion were clinical trial participation, latest advances in peritoneal and pleural mesothelioma, palliative care, early detection, genetics, coping with mesothelioma, and survivorship.

Speakers included:
Mary Hesdorffer, CRNP, Mesothelioma Applied Research Foundation
Joseph Friedberg, MD, Penn’s Abramson Cancer Center
Chi Dang, MD, PhD, Penn’s Abramson Cancer Center
Richard Alexander, MD, University of Maryland
Lee Krug, MD, Memorial Sloan Kettering Cancer Center
Andreas Rimner, MD, Memorial Sloan Kettering Cancer Center
Daniel Sterman, MD, Penn’s Abramson Cancer Center
Suzanne Walker, CRNP, MSN, AOCN, BC, Penn’s Abramson Cancer Center
Anil Vachani, MD, Penn’s Abramson Cancer Center
Joseph Testa, PhD, Fox Chase Cancer Center
Eleanor Anderson, MD, Penn’s Abramson Cancer Center

The Meso Foundation is hosting a second regional mesothelioma conference with The University of Chicago Medicine on October 10 in Chicago. To learn more about this conference, visit curemeso.org/chicago.

Common Asian Spice Shows Promise in Slowing Progression of Mesothelioma

SpicesIt has recently been discovered that the use of curcumin appears promising in slowing the progression of mesothelioma. As Medical Xpress reports, “Scientists from Case Western Reserve University and the Georg-Speyer-Haus in Frankfurt, Germany, demonstrate that application of curcumin, a derivative of the spice turmeric, and cancer-inhibiting peptides increase levels of a protein inhibitor known to combat the progression of this cancer. Their findings appeared in the Aug. 14 online edition Clinical Cancer Research.”

Medical Xpress goes on to explain, “The culprit in sparking many cancers, particularly mesothelioma, is the intracellular protein and transcription factor STAT3 (signal transducer and activator of transcription 3). A signal transducer and activator is a pathway for instructing the growth and survival of cells, and a transcription factor is a protein that controls genetic information directing cells how to perform. STAT3 is notorious for sending signals to trigger the onset of human cancers and to fuel their continued growth. The great neutralizer of STAT3 is PIAS3 (protein inhibitor of activated STAT3). PIAS3 possesses the strength to inhibit and block STAT3′s ability to cause cancer.”

As the article continues, the logistics of the study are explained in further detail. “Investigators assessed PIAS3 expression in tissue samples of mesothelioma solid tumors and the protein inhibitor’s subsequent effects on STAT3 activity. Tissue samples came from three different locations in the country, and information logged for each specimen detailed how long the patient lived and the types of mesothelioma they had. Investigators then linked the levels of PIAS3 with STAT3 activity in each sample. Additionally, investigators examined the effects of curcumin and peptides extracted from PIAS3 segments on malignant mesothelioma cells in vitro.”

Medical Xpress spoke with Afshin Dowlati, MD, a professor of medicine at Case Western Reserve University School of Medicine and the director of the Center for Cancer Drug Development at University Hospitals Seidman Cancer Center. Dowlati stated, “In those mesothelioma patients where PIAS3 is low, indeed STAT3 is activated. Mesothelioma patients who have low PIAS3 and high STAT3 have a greater chance of dying early. On the flip side, those patients with a high PIAS3 levels have a 44 percent decreased chance of dying in one year, which is substantial.”

In explaining the findings of the study, Medical Xpress continues, “Investigators also found that curcumin and PIAS3 peptides raised PIAS3 levels, which brought down STAT3 activity and caused mesothelioma cells to die. Their study served as proof of principle about the effectiveness of these two compounds in treating malignant mesothelioma, a first step in moving a treatment toward clinical trials. Additionally, their findings demonstrated that PIAS3 could serve as a predictive marker for managing mesothelioma because the disease’s tumors do not always progress in a consistent, predictable manner, even when tumor stages, grades and clinical presentations appear similar.”

Dowlati further explained the results, stating, “Our findings suggest that PIAS3 expression positively affects survival in mesothelioma patients and that PIAS3 activation could become a therapeutic strategy. Our interest for the future is that we want to find better, more simple ways to increase intracellular levels of PIAS3 for malignant mesothelioma through the use of synthetic PIAS3 peptide or curcumin analogs. We must develop a curcumin analog that is absorbable by the human body. Currently, curcumin ingested as the spice turmeric has practically no absorption within the gut.”

Visit Medical Xpress to read the full article.

The Meso Foundation Now Accepts Bitcoin Donations

BitcoinThe Meso Foundation is now accepting donations in Bitcoin, in addition to all of the traditional ways to give. The Bitcoin donation page can be found at curemeso.org/bitcoin.

“As more and more businesses are accepting Bitcoin as a form of payment, we decided it was important for us to do the same,” said Melinda Kotzian, the chief executive office of the Meso Foundation.

Bitcoin is an online-only, internet currency, started in 2009. Bitcoin donations can be easily and immediately following a donation, converted into any other currency, including the US Dollar.

“We do not want anything to stand in our way of raising funds to fund mesothelioma research, education, support, and advocacy. Our goal is to save lives, and we’ll do whatever it takes to get there,” Ms. Kotzian added.

The Meso Foundation’s bitcoin donation page can be found at curemeso.org/bitcoin.