ASCO 2023 | A morphomolecular classification of malignant pleural mesothelioma
Lynnette Fernandez-Cuesta, PhD, International Agency for Research on Cancer (IARC-WHO), Lyon, France, discusses how the introduction of a morphomolecular classification of malignant pleural mesothelioma (MPM) could impact clinical management and treatment approaches for this patient population. The recent Omics project published in Nature Genetics suggests a paradigm shift in diagnosing and treating malignant pleural mesothelioma, the findings indicating the need to move away from the current morphological classification and consider a continuum of molecular variation. The study identified four key factors, including morphology, diploidy, immune interaction, and CPG island methylation, as crucial in understanding the disease. Dr Fernandez-Cuesta emphasizes future studies should focus on validating biomarkers to incorporate these factors into clinical treatment. The tumors were classified into three phenotypes representing specialized functions: cell division, tumor immune interaction, and cell cooperation. Immunotherapies may be more effective for tumors specialized in the immune interaction, while targeted therapies require further investigation using advanced techniques like single-cell sequencing. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL.
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Transcript (edited for clarity)
So first of all, I think the the discoveries of the MESOMICS project, who which has been recently published in Nature Genetics, calls for a paradigm shift in the way malignant pleural mesothelioma is diagnosed and untreated. So what we have seen is that this we need to move forward from these three groups classification to something that includes somehow this continuum, because in fact in our data we have seen that the morphological classification only accounts for up to 10% of the molecular variation among samples and the morphological features...
So first of all, I think the the discoveries of the MESOMICS project, who which has been recently published in Nature Genetics, calls for a paradigm shift in the way malignant pleural mesothelioma is diagnosed and untreated. So what we have seen is that this we need to move forward from these three groups classification to something that includes somehow this continuum, because in fact in our data we have seen that the morphological classification only accounts for up to 10% of the molecular variation among samples and the morphological features. They only correspond to one of the four factors that we have identified being the other ones diploidy the immune interaction and the CpG methylation and CpG island methylation. And these other three factors are as important as morphology, so they cannot be just ignored. They need to be included. Having said that, we now need to design new studies that will help us validate biomarkers that could help us identify these different factors into the clinical setting in terms of treatment. What we have seen is that these four dimensions were delimited by three phenotypes that represent cancer task specialization. So the tumors were specialized either in cell division, in the tumor immune interaction and in cell cooperation. And for example, if we think about selection of populations for immunotherapies in mesothelioma is expected that those tumors that are specialized in the tumor immune interaction are more likely to respond to immunotherapies that the ones that are specialized in cell division or cell cooperation. But if we think about more targeted therapies. So here I think we need a little bit more time because the cellular processes that are underlying these different factors and these different cancer specializations are still not well understood. So we might need to go to more high, more powerful technologies like single cell sequencing to better understand these processes before we can point to some new novel targeted therapies for mesothelioma.
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