Clapper, Patti, Schweizer and Mason

Malignant mesothelioma, an asbestos induced illness, is a rare and aggressive cancer that has rapid progression, late metastases and low survival times. Primary cause of mesothelioma is exposure to asbestos. Millions of people worldwide have been exposed to asbestos and run the risk of developing this incurable malignancy. 

 

Standard methods of mesothelioma treatment, such as surgery, chemo and radiation therapy have had little effectiveness at slowing progression or extending survival times. In addition, many cases of mesothelioma are irresectable (surgery is not an option) and tumors become resistant to front line chemotherapy drugs.

 

Research efforts are continually seeking to discover new methods, interventions, drugs or combinations thereof that would slow or cure mesothelioma and other asbestos related cancers. Molecular and gene therapy approaches have found lines of study worthy of further research based upon preliminary results in clinical trials.

 

One such study recently published in the American Journal of Pathology conducted by X.B Cao and co-researchers investigated whether apoptosis and chemotherapy responses could be affected by controlling different transcription factors.   

 

Apoptosis is sometimes referred to as programmed cell death or PCD. Apoptosis plays a role in preventing cancer by inhibiting abnormalities that result in tumor development. If cancer cells interfere with normal apoptotic capabilities, then cells can continue to divide and eventually lead to tumor growth. A failure of normal apoptosis can also contribute to disease resistance to chemotherapy. 

 

Cao’s study confirmed that mesothelioma is apoptosis resistant and explored the mechanisms that lead to apoptosis failure. The study specifically looked at transcriptional control of Bcl-xl involving ETS and MET factors.   Bcl-xl are proteins that are frequently overexpressed in mesothelioma tumors and are major determinates of apoptotic homeostatis. Research is exploring if there are ways to inhibit Bcl-xl in mesothelioma cells, which would then allow normal apoptosis to occur and help in inhibiting tumor growth.

 

Cao investigated if ETS and MET factors could be employed to cause down regulation of bcl-xl in mesothelioma. ETS is one of the largest families of transcription factors and has implications in the progression of cancer.   MET stands for mesenchymal-epithelial transition. The MET oncogenes are hepatocyte growth factor receptors that encode enzyme activities.   The growth and spreading of tumors to other sites has been associated with abnormal MET activation. It has also been linked with poor prognosis.

 

Cao’s research showed potential success for inhibiting expression of tumor enhancing proteins and creating a pro-apoptotic therapy to treat mesothelioma. Further research along these lines is warranted and may lead to more effective therapeutic intervention methods.