A study recently published in the medical journal Lung Cancer investigated genetic patterns in malignant mesothelioma that contribute to the cancer’s treatment resistance in hopes of identifying new avenues for treatment.
Titled “Malignant pleural mesothelioma: genome-wide expression patterns reflecting general resistance mechanisms and a proposal of novel targets,” the study sought to observe genetic similarities among patients that make malignant mesotheliomas resistant to treatment. Further understanding the genetics behind resistance mechanisms allows scientists to develop improved and more specific mesothelioma treatments that could improve survival rates.
Researchers in this study found a close relation between gene profiles and resistance towards cancer-fighting compounds such as topoisomerase poisons, alkylating agents, antitubulines, antifolates, platinum compounds (chemotherapy) and radiation therapy. A genetic pathway, known as the Fanconi anemia/BRCA2 pathway, appeared as a key pathway in mesothelioma’s resistance to chemotherapy and radiation therapy.
Data revealed that resistance to immunotherapy could be partly explained by “leukocyte trans-endothelial migration gene down-regulation.” In addition, the study found that “Gene expression features found in other resistant cancer types related to DNA repair and replication are shared by mesothelioma and could represent general features of [tumor] resistance.”
The data is important to developing mesothelioma treatment options that are targeted to suppress the key genes and pathways that make mesothelioma resistant to treatment. Researchers found, “Targeted suppression of some of those key genes and pathways combined with chemotherapy or radiation could improve the outcome of mesothelioma therapy… Specific suppression of some genes or gene products that were discovered, could lead to improved anti-[tumor] effect of conventional chemo- and/or radiotherapy, notably microtubule related genes, cell cycle checkpoint and DNA-repair genes, with the Fanconi anemia/BRCA2 pathway as the most central.”
The authors go on to explain the implications of their results, stating, “Mesothelioma has been an unsolved oncological problem of more than 40 years with therapeutic trials, often toxic with little clinical gain. One of the lessons of this fact, supported by the present study, is that malignant mesothelioma obviously has a [heterogeneous] and complex biology with versatile resistance mechanisms. One should therefore be cautious not to start large patient studies before testing drugs of interest in various combinations on several preclinical models. There are indications that low expression of target genes, as thymidylate syntase, is related to increased drug sensitivity, an important point to bear in mind both for drug designing and testing.”
Additional information on mesothelioma and treatment options may be found through the mesothelioma Center.