The BRCA1 (breast cancer gene 1) tumour suppressor gene has been reported as a potential predictive biomarker of response to chemotherapy to antimicrotubule agents including vinorelbine, vincristine, paclitaxel and docetaxel. High levels of BRCA1 mRNA expression have been linked to better response rates and improved progression-free survival.

The data presented here highlights that BRCA1-immunonegativity can effectively predict resistance to vinorelbine and microtubule-directed chemotherapy .

Polycomb group proteins (PcG), proteins that act to regulate transcription, have been implicated in numerous aspects of malignancies especially the ones with an aggressive phenotype and in stem cell biology. Misregulation of Polycomb protein levels often leads to either a block or unscheduled activation of developmental pathways, thereby enhancing the proliferation capability of a cell. Polycomb proteins form at least two distinct complexes, the Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2). There is increasing evidence that PRC complexes have a role in tumor progression and development by blocking differentiation …

Many targeted agents, such as anti-VEGF and anti-EGFR blockers, have not shown promise against mesothelioma, at least when used as single agents. However these same targeted agents might be effective when used in combination with chemotherapy or when used in a selected subpopulation. This study tested a variety of targeted agents together with cisplatinum-pemetrexed against 4 mesothelioma lines and found vandetanib, an inhibitor of EGFR/VEGFR2/RET, to be the most effective. Although the agent has multiple effects (see figure), the effect seemed to be explained by the effect on EGFR and …

In this article, transcriptional deregulation, mediated by inactivation of the nuclear deubiquitinase BAP1, is implicated in the pathogenesis of mesothelioma.  The two most common known genetic alterations in mesotheliomas are 9p21 deletions on CDKN2A and 22q deletions causing NF2 loss. The authors show that another gene with a high rate of non-synonymous mutations is BAP1 (encoding BRCA1-associated protein 1).  Somatic mutations were found in 23% of mesotheliomas.  The study also shows that other common tumor suppressors, such as PTEN and p53, showed few or no mutations, confirming data from previous …

In this short communication, the authors focus on the SRC pathway, which is hyperactivated in MM specimens and cell lines compared with normal mesothelial cells (Menges et al., 2010). Inhibition of the SRC pathway with the multi-targeted inhibitor dasatinib has been shown to result in apoptosis, cell cycle arrest and decreased migration and invasion in mesothelioma cell lines (Tsao et al., 2007).
Here the authors test a panel of newly synthesized pyrazolo[3,4-d]pyrimidine derivative SRC kinase inhibitors, that bind the ATP pocket of the SRC kinase, which effectively inhibit SRC activity at nanomolar concentrations.

Here is a paper by Deborah Altomare analyzing Ink4A and Arf role in mesothelioma pathogenesis.
p16(INK4A) and p14(ARF) are frequently co-deleted in human malignant mesothelioma and the authors here find that in vivo both CDKN2A/ARF gene products suppress asbestos carcinogenicity. Furthermore, while the inactivation of Arf appears to be crucial for mesothelioma pathogenesis, the inactivation of both p16(INK4A) and p19(ARF) cooperate to accelerate asbestos-induced tumorigenesis.

Here is a paper analyzing the intriguing possibility that epigenetic drugs may increase the immunogenic profile of mesothelioma, thereby enhancing the ability of an immune response to target the tumor. 
HDAC inhibitors and demethylating agents open the chromatin into a conformation that facilitates transcription not only of tumor suppressors but also of tumor antigens, such as NY-ESO-1, MAGE-A1 and MAGE-A3. 

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 …