The Mesothelioma Applied Research Foundation is calling for applications for its 2012 round of mesothelioma research grant funding. Continuing its efforts to stimulate translational research for the treatment of malignant mesothelioma, the Meso Foundation is again soliciting applications for funding of innovative projects that address issues for the treatment of the disease.

Mesothelin is currently considered the best available serum biomarker for malignant pleural mesothelioma. To examine the reported diagnostic accuracy of mesothelin and evaluate its value for early diagnosis, the authors performed a meta-analysis on the individual patient data (IPD) of 16 diagnostic studies, representing a total of 4,491 individuals, including 1,026 patients with malignant pleural mesothelioma.
They found a significant heterogeneity in reported diagnostic accuracies of mesothelin (see Figure for sensitivity of mesothelin in different studies). Differences in study population can explain this heterogeneity, since the type of control group, mesothelioma …

A recent publication by Sekido and colleagues has highlighted the connection between two relevant survival/growth pathways in mesothelioma, TGF-beta and NF2/Hippo.

TGF-beta may play important roles in the immune regulation of mesothelioma and in the production of extracellular matrix.
NF2 (neurofibromatosis type 2; Merlin) gene or downstream signaling molecules of the Hippo signaling cascade contain inactivating mutations in nearly 75% of MM cases.

This article presents the results in humans of the first intrapleural instillation of a genetically modified cell line carrying a thymidine kinase suicide gene in mesothelioma.  From prior work, these instilled cells are thought to adhere to the intrapleural tumor and to form gap junctions.  Then, a pro-drug, ganciclovir, is delivered intravenously, diffuses into the pleural space and is converted by the TK gene in the cells to a toxic drug, ganciclovir-triphosphate, which kills the instilled cells and neighboring tumor cells via a ‘bystander effect’.  The process may also induce …

Although inhibition of EGFR has not shown promise in clinical trials of mesothelioma, broader inhibition of growth pathways might be more effective.  In this study, mesothelioma cells were propagated from human mesothelioma tumors of different histologies and found to have activation of several receptor tyrosine kinases.  In the figure, one sees an array from one mesothelioma cell line with evidence of activation of EGF-R, ERBB3, IGF1R, AXL, and MET, not seen in the normal mesothelial cells.  (The two spots in each corner are positive controls)  Inhibition of a chaperone protein …

In this retrospective study by Italian and Dutch researchers, mesothelioma samples from 99 patients treated with carboplatin and pemetrexed were analysed for markers of clinical outcome.
A low level of protein expression of thymidylate synthase (TS), the major folate-dependent enzyme inhibited by pemetrexed, correlated with improved outcome: better disease control, longer progression free survival and longer overall survival. In contrast, the level of protein expression of ECRR1, an excision repair gene associated with platin resistance in some tumors, did not. This study is the first to show that …

Here is an interesting article by Dr Hassan reporting the results of a phase I clinical trial of the chimeric anti-mesothelin monoclonal antibody MORAb-009.
Mesothelin is expressed on the surface of many different cancer cells, particularly in the epithelioid type of mesothelioma.  Mesothelin provides a target for anti-mesothelin antibodies.  At least 2 treatment strategies are being tested currently, the SS1P (a recombinant immunotoxin with anti-mesothelin Fv linked to a truncated Pseudomonas exotoxin) and the MORAb-009 (a high-affinity monoclonal antibody, a chimera between mouse Fv and human IgG1/k Fc).  The MORAb-009 may …

An article by Dr Hedy Kindler unraveling the path to a better diagnosis and treatment of malignant mesothelioma. Here she analyses the latest findings in chemotherapy, targeted agents, biomarkers and delineates the therapeutic research opportunities for the future.

Daniel H Sterman MD and Steven M Albelda MD.
University of Pennsylvania Med Ctr, Philadelphia, USA.
Read here: 2006 January Vol4 Issue1