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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
Biomarker-guided targeted and immunotherapies in malignant pleural mesothelioma
Haitang Yang1, Duo Xu1, Ralph A Schmid2
1Division of General Thoracic Surgery, Department of BioMedical Research (DBMR), Inselspital, Bern University Hospital, University of Bern, Switzerland.
Abstract:
Malignant pleural mesothelioma (MPM) is a lethal thoracic malignancy whose incidence is still increasing worldwide. MPM is characterized by frequent inactivation of tumor-suppressor genes (TSGs), e.g., the homozygous deletion of CDKN2A/2B and various genetic alterations that inactivate BAP1, NF2, LATS1/2, and TP53. The leading cause for the poor prognosis of patients with MPM is the lack of effective treatment options, with conventional chemotherapy being the standard of care in the clinic, which has remained unchanged for almost 20 years. Precision oncology, a burgeoning effort to provide precise cancer treatment tailored to unique molecular changes in individual patients, has made tremendous progress in the last decade in several cancers, but not in MPM. Recent studies indicate a high degree of tumor heterogeneity in MPM and the importance to optimize histological and molecular classifications for improved treatment. In this review, we provide an up-to-date overview of recent advances in MPM by focusing on new stratifications of tumor subgroups, specific vulnerabilities associated with functional loss of TSGs and other biomarkers, and potential clinical implications. The molecularly based subdivisions not only deepen our understanding of MPM pathobiology, but more importantly, they may raise unprecedented new hopes for personalized treatment of MPM patients with biomarker-guided targeted and immunotherapies.
Insights
Malignant pleural mesothelioma (MPM) treatment lags behind other cancers. New molecular subtypes and biomarkers offer hope for personalized therapies and improved patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer with increasing incidence and poor prognosis.
- Current treatment options, primarily conventional chemotherapy, have shown limited efficacy for nearly two decades.
- Tumor-suppressor gene inactivation (e.g., CDKN2A/2B, BAP1, NF2, LATS1/2, TP53) is a hallmark of MPM, contributing to its lethality.
Purpose of the Study:
- To review recent advances in understanding MPM, focusing on molecular classifications and therapeutic vulnerabilities.
- To highlight the potential of precision oncology approaches for MPM treatment.
- To discuss the clinical implications of novel MPM stratifications and biomarkers.
Main Methods:
- Review of current scientific literature on Malignant Pleural Mesothelioma.
- Analysis of recent studies on MPM tumor heterogeneity and molecular alterations.
- Synthesis of data on tumor-suppressor gene functions and biomarker identification.
Main Results:
- MPM exhibits significant tumor heterogeneity, necessitating refined classification systems.
- Specific vulnerabilities are linked to the functional loss of tumor-suppressor genes and other biomarkers.
- Molecularly-based subdivisions of MPM are emerging.
Conclusions:
- Understanding MPM pathobiology through molecular subdivisions is crucial.
- Biomarker-guided targeted and immunotherapies hold promise for personalized MPM treatment.
- Recent advances offer new hope for improving outcomes in MPM patients.
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