Basic Research
Our strategic approach has been to build an integrated research effort among multiple disciplines, with each contributing to a different aspect of the research program. All projects share access to patients (with consent), clinical samples, and a central database of patient and research data. Each project is ultimately designed to improve patient diagnosis, prognosis, therapy and outcome.
The following are summaries of current International Mesothelioma Program (IMP) research projects. Click on the title to read more on each.
Identifying Mesothelioma-Related Mutations
IMP scientists have discovered the unique genetic mutations of multiple mesothelioma tumors from individual patients. They found that each tumor had its own unique mutational profile – its own genetic fingerprint. In the not-too-distant future, the ability to obtain this unique genetic fingerprint will improve therapeutic decisions for every cancer patient. This is the first time researchers anywhere have identified in an unbiased manner all of the mutations associated with any cancer.
Novel Therapeutics Laboratory Identifies Innovative Approaches to Mesothelioma Treatment
Scientists in the Novel Therapeutics Laboratory seek to explain the mechanisms of action of mesothelioma and of the chemotherapeutic agents used to combat it. Their goal is to identify opportunities to improve treatment. Recent work has investigated the effects of cisplatin and rapamycin, alone and together, on six mesothelioma cell lines. Results in cell lines indicate that the combination of the two drugs significantly increased tumor cell death compared with either drug alone. In the coming years, Novel Therapeutics Laboratory investigators will continue the search for agents that may provide the basis for innovative, safe, and effective therapies.
Novel Testing Model Studies Effects of New Mesothelioma Drugs
Our researchers are beginning to investigate a promising new drug for mesothelioma, using a novel, more clinically relevant model for testing response to chemotherapeutic drugs. The IMP has worked on a project to study the drug bortezomib (Velcade®) and all cancer-related proteins within the cell that bortezomib interacts with and affects, in cultured mesothelioma cell lines. Our researchers demonstrated that bortezomib increases the ability of the chemotherapy drugs cisplatin and pemetrexed (Alimta®) to cause cell death in mesothelioma cell lines. This suggests that bortezomib alone or in combination with standard chemotherapy may improve outcomes for patients with malignant pleural mesothelioma.
Epidemiology of Malignant Mesothelioma
The goal of this project is to conduct a comprehensive epidemiologic study of mesothelioma to investigate the underlying causes of the disease. It uses detailed patient questionnaires and tumor profiling to assess genetic susceptibility factors that may contribute to mesothelioma.
Innovative Test Will Help Physicians Customized Mesothelioma Therapy
IMP researchers have developed and validated a gene-ratio test that uses expression levels of four genes associated with mesothelioma to predict whether an individual patient is likely to benefit from standard multi-modality mesothelioma therapy. When combined with other patient-specific information, the test allows surgeons to predict with high certainty which patients will respond favorably to surgery and which should consider more aggressive experimental therapy. The information will be valuable in driving physicians’ recommendations for therapy.
Kinase Targets in Mesothelioma
The overall aim of this project is to discover oncogenic kinase targets (both receptor and non-receptor tyrosine kinases), and to determine whether such kinases serve as appropriate therapeutic targets for patients with mesothelioma. This project is highly translational in that the objective is to identify drug targets that are evaluable in the near-term in clinical trials.
Innovative Technique Enhances Mesothelioma Research
Scientists from the IMP’s mesothelioma tumor and tissue bank have pioneered an innovative method for characterizing frozen tissue samples with an unprecedented level of precision. This technique, known as microaliquoting, involves making very thin slices throughout a frozen tissue sample and examining them under a microscope to determine the percentage of tumor cells. Microaliqoting represents the next generation of prospective quality analysis for frozen tissue samples. Because of its precision in tissue characterization, it can play a valuable role in molecular research aimed at improving treatment for mesothelioma and other diseases.
Role of Asbestos in Development of Mesothelioma
Although asbestos is the only substance consistently associated with the development of mesothelioma, many questions remain as to the mechanisms by which it causes malignancy and whether there are, in fact, other currently unrecognized substances that also contribute to mesothelioma. IMP researchers are studying concentrations of fiber types in patients with mesothelioma to define the fiber types that contribute to the disease and how their presence in the body might trigger the development of mesothelioma.
Quality of Life Enhancement for Mesothelioma Patients
A newly-reopened IMP-funded study seeks to describe a quality-of-life “baseline” for mesothelioma patients, identify those factors that enhance and those that inhibit quality of life, and determine the impact of different treatment regimens (multimodality treatment, chemotherapy alone, other treatment, and supportive care) on patients’ quality of life.
Improved Staging and Prognosis
Staging of mesothelioma is challenging. Unlike other malignancies, staging does not provide reliable prediction of survival probability for individual mesothelioma patients. IMP researchers have used the central database to identify novel patient characteristics related to outcomes, leading to proposed modifications of staging criteria and stage-independent risk assessment. These improvements may provide patients with more personalized profiles when considering the risks and benefits of different treatment options as related to their own priorities.
