Mesothelioma and Murine Models of Melanoma and Adenocarcinoma

Another interesting study is called, "Efficacy of CD40 Ligand gene therapy in malignant Mesothelioma" - American Thoracic Society, New York, NY, ETATS-UNIS  (1989) (Revue).  Here is an excerpt: "Abstract - Gene delivery of CD40 Ligand (CD40L) has shown promise in murine models of melanoma and adenocarcinoma; however, its potential for thoracic malignancies such as malignant mesothelioma remains unclear. In this study, we investigated the hypothesis that CD40L gene therapy would be effective in local and distant tumor suppression in mesothelioma using an immunocompetent murine model. Using a recombinant adenovirus encoding murine CD40L (AdCD40L), we demonstrated no suppression of in vitro cell growth for the AC29 (mesothelioma) cell line. However, inoculation of immunocompetent CBA/J mice with AC29 cells treated ex vivo with AdCD40L resulted in significant suppression of tumor formation in vivo when compared with controls (P < 0.001). Intratumoral inoculation of AdCD40L into previously established AC29 tumors yielded similar antitumor results and was associated with increased recruitment of intratumoral CD8+ T cells. Adoptive transfer of CD8+ T cells from AdCD40L-treated tumor bearing mice conferred protection to naive mice given an AC29 tumor challenge. Finally, in mice with two synchronous tumors, treatment of one of the tumors with AdCD40L resulted in a regression of both tumors. These findings demonstrate the development of tumor specific CD8+ T cells by AdCD40L and support the further development of AdCD40L for the treatment of malignant mesothelioma."

Another interesting study is called, "The Use of Chemotherapy in Patients with Advanced Malignant Pleural Mesothelioma: A Systematic Review and Practice Guideline" by Ellis, Peter MBBS, PhD, FRACP; Davies, Angela M. MD, FRCPC; Evans, William K. MD, FRCPC; Haynes, Adam E. BSc; Lloyd, Nancy S. BSc; the Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
Journal of Thoracic Oncology: July 2006 - Volume 1 - Issue 6 - pp 591-601.  Here is an excerpt: "Abstract - Background: This clinical practice guideline, based on a systematic review, was developed to determine which chemotherapeutic agents (or combinations of agents) show the highest response rates, improved survival, quality of life, or symptom control in patients with advanced malignant pleural mesothelioma.

Methods: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials, published as articles and abstracts, were selected and assessed. External feedback was obtained from Ontario clinicians, and the guideline was approved by the provincial Lung Cancer Disease Site Group.

Results: One hundred nineteen studies were eligible, including eight randomized trials and 111 phase II trials. The pooled response rates from phase II trials suggest that response rates with combination chemotherapy are higher than with single agents. Data from the largest randomized controlled trial demonstrated that chemotherapy with cisplatin and pemetrexed significantly improves response rates (41% versus 17%, p < 0.001), time to progression (5.7 months versus 3.9 months, p = 0.001), and overall survival (median, 12.1 months versus 9.3 months, hazard ratio = 0.77, p = 0.020) in comparison to single-agent cisplatin. A second trial demonstrated cisplatin and raltitrexed significantly improved median survival compared to single-agent cisplatin (11.4 months versus 8.8 months; hazard ratio = 0.76, p = 0.0483). Overall response rate (24% versus 14%, p = 0.056) was greater in the combination treatment arm, but this difference was not statistically significant.

Conclusions: There is good evidence to recommend chemotherapy with pemetrexed and cisplatin for adult patients with symptomatic advanced malignant pleural mesothelioma. Such treatment should be administered with supplementation of vitamin B12 and folic acid. If pemetrexed is not available, cisplatin plus raltitrexed is a reasonable alternative."

Another interesting study is called, "New Agents in the Management of Advanced Mesothelioma" by Nicholas J. Vogelzanga, Camillo Portabd, Luciano Mutticd -
Volume 32, Issue 3, Pages 336-350 (June 2005).  Here is an excerpt: "Malignant pleural mesothelioma (MPM) is a seemingly uncommon tumor whose incidence has in fact increased steadily and progressively over the last 30 years. Indeed, an actual "epidemic" is expected in Europe over the next 20 years. Despite unquestionable improvement in the diagnostic methods at our disposal and the availability of new treatment strategies, the prognosis of MPM patients remains dramatically poor (12 to 18 months' median survival from diagnosis), although exceptional cases of long-survivors are reported in all literature series. The current review will cover the dramatic improvements in the treatment of this rare disease that have been recently achieved, as well as the promise that new, molecular-targeted therapies, such as bortezomid, mTOR (mammalian target of rapamycin) inhibitors, and Met inhibitors, seem to offer for the next few years. With pemetrexed we now have a drug that is able to impact patient survival. Together with the newer drugs, rapidly emerging from the laboratory to be applied in the clinic, we have the hope of making further advances in the struggle against this disease."

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.