The expression of chemokines and chemokine receptors has been linked to disease prognosis of various cancers.  The expression and role of chemokines and their receptors in mesothelioma is not well known.  In this article by Tong Li et.al, the authors report that the chemokine CXCL12 (stromal derived factor 1) and the receptor CXCR4 were overexpressed in mesothelioma samples from 41 patients and in cell lines.  CXCR4 was found in almost all mesotheliomas (97%) and CXCL12 in 78%; another receptor CXCR7 was only weakly expressed. CXCL12 binding to CXCR4 may mediate …

The chemoresistance of solid tumors such as mesothelioma may be better studied in vitro 3D models because multicellular spheroids acquire multicellular resistance that may recapitulate the stubborn chemoresistance seen in vivo.
Dr. Xiang et al. recently used multicellular spheroids to test the efficacy of the recombinant anti-mesothelin immunotoxin SS1P in spheroids. The authors compared 2D (monolayer) and 3D (multicellular spheroid) mesothelioma cultures of the cell line NCI-H226 and found that, regardless of equal mesothelin expression in 2D and in 3D, SS1P was at least 100 times less cytotoxic in spheroids compared …

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 …

Here is a paper by Dr Shukla et al. addressing the role of the MAPK ERK 1/2 activity in mesothelioma resistance to doxorubicin.
Treatment of mesothelioma cells with doxorubicin phosphorylates and activates ERK1/2.  Mesothelioma cells are also shown here to upregulate key chemoresistance genes, regulated by ERK1/2, such as Bcl-2, cFos and BRCA1. Blockade of ERK 1/2 activity with the kinase inhibitor UO126 resulted in increase citotoxicity in combination with Doxorubicin. Moreover, UO126 significantly reduced the transcription levels of Bcl-2 and BRCA1, further supporting a role for ERK 1/2 activity in …

The Nf2 gene is mutated in 40% of mesotheliomas and and disruption of the Nf2/Merlin signaling is key to Anton Berns’ murine mesothelioma model. The authors here propose that Merlin suppresses tumorigenesis by translocating to the nucleus and by inhibiting CRL4(DCAF1), an E3 ubiquitin ligase. This breakthrough finding opens up a new candidate drug target for the treatment of NF2 tumors – especially because many patients have gene mutations that affect this cell signaling pathway at various levels.