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