The progression and evolution of cancer genomics is giving us unprecedented insight into malignancies. Most recently, a paper on acute myeloid leukemia and one on endometrial carcinoma, part of an ambitious project by the National Institutes of Health to scrutinize DNA aberrations in common cancers, have highlighted that cancer will increasingly be seen as a disease defined by its genetic fingerprint rather than by the organ where it originated.

Though long considered the gold-standard for diagnosing cancer, customary pathological approaches are not always successful.

Here, De Rienzo and colleagues applied the bioinformatic technique of gene-expression ratio tests to develop and validate molecular signatures for the differential diagnosis of mesothelioma (MPM) as proof of principle of the applicability of this technique to cancer diagnosis.

Early detection of mesothelioma is key for chemo-efficiency. The authors conducted a multi-center case-control studies in serum from 117 mesothelioma cases and 142 asbestos-exposed control individuals. Biomarker discovery, verification, and validation were performed using the SOMAmer proteomic technology, which simultaneously measures over 1000 proteins in unfractionated biologic samples. Using univariate and multivariate approaches they discovered 64 candidate protein biomarkers, consisting of both inflammatory and proliferative proteins, processes strongly associated with asbestos-induced malignancy. The author further selected a pool of 13 candidate proteins (classifiers) for distinguishing mesotheliomas from controls. The ability of the classifiers …

This publication represents an update to the iMig guidelines that were first published in 2009, following the iMig meeting held in Chicago (Oct. 2006). This update is meant to be a practical guide for pathologists and presents consensus views on diagnosis and the common pitfalls to be avoided.
 

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 …