The Journey of a Mesothelioma Research Study

When patients and their families need help following a diagnosis or throughout treatment, the Meso Foundation is there for them – day or night.

Researcher

But getting patients and their families through the immediate treatment is only one side of tackling this disease. At the Meso Foundation, we believe that research into new treatments is fundamental to eradicating mesothelioma and the suffering caused by it. In fact, our mission statement emphasizes that the Foundation must “fund the highest quality and most promising meso research projects from around the world through rigorous peer review.”

Yesterday, the Meso Foundation released the important news that, this year, researchers from across the world submitted 48 proposals for funding (22 applications were from international applicants). In the next week, we will divide the number of submitted proposals among our Science Advisory Board (SAB) members and assign approximately 7 to 10 proposals to each reviewer, and 2 to 3 reviewers to each proposal.

Our SAB is made up of scientists and doctors from around the world, who have devoted their lifework to researching mesothelioma, making them the peers of our applicants, thus making our review a peer review.

We placed the adjective “rigorous” into the sentence describing our peer review, because it truly is.  The review process consists of scoring and critiquing each and every application submitted. Below are a few examples of the detailed questions each reviewer is asked when reviewing a proposal.

  • Does the project address an important problem or a critical barrier to progress in the field?
  • How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
  • Are the PD/PIs, collaborators, and other researchers well suited to the project?
  • Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?
  • Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?
  • Will the scientific environment in which the work will be done contribute to the probability of success?

The reviewers must then score each proposal according to these questions, on a scale of 9 to 1, with 1 being the highest possible score. In September, these scores will be collected and the proposals ranked accordingly. Only the top half of the total number of proposals will pass this stage and move to the next, where they will be scrutinized further in depth.

At this point, we select SAB members who are experts in the fields of those applicants whose projects have advanced. This ensures that the proposals are evaluated by someone who can speak to the plausibility and soundness of the hypothesis submitted, which, in turn, ensures that our funding be awarded to the most promising projects.

Following the second round, the proposals are once again scored and ranked. Based on this line-up, each remaining application is opened for discussion by the entire SAB. We hold a conference-call in November to facilitate this discussion and we come away with a solid list of top 10 projects. This list is presented in January to the Board of Directors, which selects proposals for funding. This decision is based on the critiques and ranking received from the SAB, and the financial capability of the Foundation.

At the end of this process, an approved application will have moved through three review cycles, be assessed by no less than 6 SAB members, be scrutinized by at least one expert within its specific field, and approved by the two governing bodies of the organization.

This is, no doubt, a relatively long and labor-intensive process, but it is a necessary one to make sure that the limited funds available for research are spent responsibly only on the most promising and the highest quality studies. As a nonprofit organization, we have an obligation to our patients, constituents and donors to make the most of their donations and support, and with this review model, we believe to fulfill and exceed all expectations.

EPHB2 as a New Treatment Target for Mesothelioma

MesoSym-0150_smallLast week, the Journal of Thoracic Oncology published the results of a study looking into the overexpression of the ephrin B2 receptor (EPHB2) in patients with mesothelioma. The researchers at the New York University Langone Medical Center observed that EPHB2 is overexpressed in all malignant mesothelioma cell lines, but not in benign mesothelial cells. In addition, they found that silencing this receptor resulted in a significant increase in certain processes responsible for naturally ridding the body of old and defective cells (including cancerous ones).

The team of researchers who worked on this study includes Dr. Harvey Pass, one of the founders and a former board member of the Mesothelioma Applied Research Foundation. Dr. Pass has been a leader in the field of mesothelioma and a vocal advocate for mesothelioma patients.

“The mesothelioma community is looking for novel targets for therapy, and the data on the ephrins may provide an opportunity for this,” said Dr. Pass. “Certainly we also must expand our findings to elucidate the prognostic and predictive characteristics of this important pathway,” he added.

Support future research efforts. Donate to the Mesothelioma Applied Research Foundation today.

Mesothelioma Included in Department of Defense Spending Bill

cdmrp_logoEarlier this month, the House Appropriations Committee passed the FY2014 Defense Appropriations Bill, which included mesothelioma as a topic area in their Peer Reviewed Cancer Research Program for the third year.  Mesothelioma researchers will be eligible to apply for $15 million in research funding.

Mesothelioma has been included on the list of diseases eligible to receive funding through the Department of Defense’s Congressionally Directed Medical Research Program (CDMRP) since Fiscal Year 2008. The CDMRP has funded a total of $8.9 million in mesothelioma research to date. In Fiscal Years 2008, 2009, and 2010 it was included in the Peer Reviewed Medical Research Program (PRMRP) to compete for $50 million dollars.

In 2011, due to the advocacy of the mesothelioma community, it was moved to the Peer Reviewed Cancer Research Program (PRCRP), to compete with a smaller number of topic areas for $16 million.  In 2012, this sparse amount of funding was decreased to $12.8 million. It returned to $16 million in 2013. The $15 million included in the House Defense Bill is slightly more than a 6% cut from the 2013 amount.

“We are pleased that the advocacy of the mesothelioma community has continued to secure this funding for mesothelioma for the 7th consecutive year,” said the executive director of the Mesothelioma Applied Research Foundation, Mary Hesdorffer, Nurse Practitioner.  “We commend Congress for recognizing the increased risk of developing mesothelioma for our service men and women and continuing to fund this much needed research.”

This bill will next move to the House Floor, and then on to the Senate. The Meso Foundation will continue to follow the appropriations process, so stay tuned for more information.

Update from The American Society of Clinical Oncology (ASCO) Annual Meeting

By Lee Krug, MD, Memorial Sloan-Kettering Cancer Center

ASCO-2013_1The American Society of Clinical Oncology meeting was held from June 1-4 in Chicago. This is the largest oncology meeting each year with around 30,000 attendees from all over the globe who congregate to discuss the latest research in all cancer types. I thought I would summarize a few of the presentations that were made regarding mesothelioma.

Accelerated hypofractionated hemithoracic intensity modulated radiation therapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma (IMRT)

This study was presented by Dr. Marc de Perrot from Toronto, a member of our Science Advisory Board. In this approach, patients with early stage mesothelioma are treated first with high dose radiation over one week, and then, after one week of rest, patients then undergo an extrapleural pneumonectomy (EPP). If patients were found to have mediastinal lymph nodes at the time of surgery, they were planned to get chemotherapy afterward. This was a select group of patients who participated since only 18% of the patients with mesothelioma seen at the center over 4 years were enrolled on this study. Amazingly, the complications after the surgery were not more than expected, though one patient did die of an infection. Furthermore, the survival rates were quite promising; for patients with epithelioid subtype, 85% were predicted to be alive after 3 years. This is a high risk, aggressive treatment modality appropriate for only a select group of patients, and more follow up is needed. However, the excellent survival results are notable.

Randomized phase II study adding axitinib to pemetrexed-cisplatin in patients with malignant pleural mesothelioma

This was a trial conducted at a single institution in the Netherlands.  The researchers were aiming to find a drug that would improve the results of standard Pemetrexed (Alimta) and cisplatin chemotherapy. In this study, another drug called axitinib was added to that chemotherapy combination. Axitinib is an oral drug that blocks the vascular endothelial growth factor receptor (VEGFR) which is responsible for the formation of new blood supply to feed the tumor, which contributes to tumor growth. Patients were placed in two groups, one-third receiving treatment with pemetrexed and cisplatin alone, and two-thirds receiving the same chemotherapy plus axitinib. Patients received three cycle of therapy, and then underwent a pleurectomy (PD). The rate of tumor shrinkage and survival times were no different with the addition of axitinib, but the trial was quite small with only 31 patients in total, so it is difficult to draw definitive conclusions.

Phase I study of cediranib in combination with cisplatin and pemetrexed in chemonaive patients with malignant pleural mesothelioma

Dr. Anne Tsao from MD Anderson (another member of our Science Advisory Board) presented the results of this study on behalf of the Southwest Oncology Group. This study had a similar goal, to find a drug that could be added to standard chemotherapy. Like axitinib, cederinib is a pill that blocks the VEGF receptor, but it also blocks another growth factor called platelet derived growth factor receptor (PDGFR).  This study was designed to determine the side effects of that treatment and find the best dose. Twenty patients received the combination, and two doses of cederinib were tested. Patients received 6 rounds of chemotherapy plus cederinib, and then stayed on cederinib as a maintenance therapy after that. At the higher dose, two patients had severe diarrhea, two had debilitating fatigue, and one had confusion, so the lower dose was chosen for further study. Although the number of patients with tumor shrinkage was not impressive, the time before the cancer grew again was much longer than usual. A larger study is now ongoing in which patients are randomized, some receiving chemotherapy alone and some with chemotherapy plus cederinib.

Sensitivity of malignant mesothelioma lacking Merlin to the FAK inhibitor VS-6063: Evaluation of merlin/NF2 status in clinical samples

One of the genes that is commonly mutated in mesothelioma tumors is NF2 “(neurofibromin 2) This gene makes a protein called Merlin. Merlin sends growth signals inside the cancer cell and one of the proteins it interacts with is focal adhesion kinase (FAK). This abstract reported on experiments in the laboratory. The researchers treated mesothelioma cancer cells and also tumors in mice with a drug that blocks FAK called VS-6063. The treatment worked best in tumor cells that had NF2 mutations supporting their hypothesis. They have used this information to plan a large randomized trial with VS-6063 that is set to start this summer. Patients who have completed initial treatment with chemotherapy will be randomized to receive VS-6063 or placebo, to see if this drug delays the time before the cancer will start to grow again.

2013 Grant Cycle Has Been Opened Up to Mesothelioma Researchers

researchThe Mesothelioma Applied Research Foundation (Meso Foundation) announced the opening of its 2013 Mesothelioma Grant Cycle to researchers across the United States and the world. Each grant is worth $100,000. To date the Meso Foundation has awarded over $8.2 million in research funds.

Researchers are invited to submit applications by visiting proposalCENTRAL’s website. There, they will find the listing for the Mesothelioma Applied Research Foundation along with submission instructions. Applications are limited to 10 pages (not including biographies) and are due no later than August 2, 2013. Final award decisions will be made in December 2013 and all applicants will be notified of the outcome.

Eligible projects may relate to benchwork, translational or clinical research that is not presently funded or pending review and may be conducted through any not-for-profit academic, medical or research institution. The Meso Foundation will review and monitor the project’s progress and results, requiring semi-annual disposition of funds reports, a ten-month progress report, a presentation at the Foundation’s Symposium and a full progress report at the close of the project.

Projects will be considered for funding by the Meso Foundation’s Science Advisory Board, whose members are published and esteemed doctors and researchers within the field of mesothelioma.

More information about the grants program and projects funded since 1999 can be found on the Meso Foundation’s website.