Today is a first for this blog--a guest post! I recently was contacted by Danielle DiPietro, National Awareness Director for the Mesothelioma Center at Asbestos.com to see if I might be interested in a guest blog. What follows is a brief review of new biomarkers for mesothelioma. It seems that the search for novel (and better) biomarkers for mesothelioma, especially for early diagnosis and pathological confirmation, has been going on for years. It has. And mesothelioma hasn't gotten any easier to diagnose. And it continues to be have a miserable prognosis. Michelle Llamas, a writer for the Mesothelioma Center, wrote what follows and I hope that you all find this informative. I invite you, whether you may be a physician, patient, or interested person to explore their Website--I find it very informative and hopeful. On behalf of the Mesothelioma Center and myself, we would appreciate any comments that you might generously offer.
New Mesothelioma Biomarkers
Mesothelioma remains incredibly difficult to diagnose and treat. While a biopsy is the most accurate method of diagnosing mesothelioma, biomarkers are being researched for the purposes of improving early stage diagnosis and for evaluating the effectiveness of treatment.
There are several mesothelioma biomarkers currently being studied. Each biomarker is tested for sensitivity and specificity in detecting the mesothelioma cancer cells. Some of the current markers include:
- calretinin (CALB2)
- cytokeratin 5
- epithelial membrane antigen (EMA)
- megakaryocyte potentiating factor (MKPF)
- osteopontin (OPN)
According to a panel of expert pathologists from the International Mesothelioma Interest Group, guidelines for diagnosing mesothelioma and differentiating it from adenocarcinoma or other tumors requires use of a marker with a sensitivity of 80 percent or more. Unfortunately, the majority of biomarkers lack sensitivity. Some research suggests using a combination of biomarkers to achieve better sensitivity and specificity.
In recent studies mesothelin and CA-125 have proven to be among the most promising biomarkers with implications for both diagnosis and treatment.
Perhaps one of the most significant recent developments in biomarker research has been the discovery of elevated mesothelin levels in malignant mesothelioma patients. Found in normal mesothelial cells, mesothelin is a cell-surface glycoprotein.
In studies that compared mesothelin to osteopontin and megakaryocyte potentiating factor, mesothelin was found to be the best biomarker for mesothelioma.
Assays of mesothelin may be used as an indicator of disease progression since higher levels of this marker are present in more advanced stages of the disease. Testing for mesothelin levels in a patient’s blood cannot currently replace biopsy or cytologic diagnosis, but this type of testing may be applicable when a patient’s health precludes them as a biopsy candidate.
CA-125 is an antigen that is shed by tumors. Though this marker has no benefit in differentiating mesothelioma from other forms of cancer, several studies have shown that it can be valuable as a method to gauge effectiveness of treatments as well as track the progression of the disease.
In a study of patients that underwent debulking surgery, the levels of CA-125 fell sharply in contrast to those who did not undergo the surgery. Furthermore, levels of the marker increased in patients who developed progressive disease after surgery and other treatments.
Advances in Mesothelioma Treatment Using Biomarkers
Biomarker research continues to yield promising advances for the treatment of mesothelioma.
One such advancement is the use of mesothelin to develop the first commercially marketed in vitro diagnostic test for mesothelioma, the MESOMARK® test. This manual enzyme-linked immunosorbent test measures the levels of Soluble Mesothelin-Related Peptides (SMRP) released by cancer cells, improving the chances for early diagnosis.
In 2010, the results of a Phase I clinical trial revealed that a mouse-human chimeric monoclonal antibody called MORAb-009 could kill mesothelin-expressing cell lines through creating cellular cytotoxicity.
The study also suggested that mesothelin was a receptor for CA-125 and that the binding of these two markers may signal tumor metastasis. Applying the MORAb-009 antibody to these cells prevents binding which may also inhibit tumor metastasis to improve patient survival rates.
Bio: Michelle Y. Llamas is a writer for the Mesothelioma Center. She is committed to generating mesothelioma awareness and providing information regarding breakthroughs in mesothelioma treatment.
Fujirebio Diagnostics, Inc. (2008). Mesomark. Retrieved from http://www.fdi.com/mesomark/world/home.html
Hassan, R., Schweizer, C., Lu, K. F., Schuler, B., Remaley, A. T., Weil, S. C., & Pastan, I. (2010). Inhibition of mesothelin-CA-125 interaction in patients with mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapy. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864325/?tool=pubmed
Mott, F. E. (2012). Mesothelioma: A review. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22438785
Pass, H. I., Vogelzang, N. J., & Carbon, M. (Eds.). (2005). Malignant mesothelioma: Advances in pathogenesis, diagnosis, and translational therapies. New York: Springer.
Tannapfel, A. (Ed.). 2011. Malignant mesothelioma: Recent results in cancer research. New York: Springer.