Estrogen receptor beta (ERβ) expression in different subtypes of malignant pleural mesothelioma

Background: Estrogen receptor beta (ERβ) is a potential target for cancer therapy as a tumor suppressor. Malignant pleural mesothelioma (MPM) is a rare but fatal cancer. This study tries to estimate the incidence of ERβ expression in the various subtypes of MPM tumors. Methods and Materials: In a retrospective study performed at a pulmonary tertiary referral hospital, formalin-fixed paraffin-embedded human tissues of 46 definitive MPM were evaluated for expression of ERβ by immunohistochemistry. Results: ERβ was detected in 14 cases (30.4%) out of the total 46 patients with a mean age of 58.08±11.59 SD, including 33 (71.7%) males. There was no statistically significant difference in patients with positive ERβ staining versus negative cases in age and sex (P >0.05). MPM subtypes included 36 (78.2%) cases of epithelioid mesothelioma, 3 (6.5%) cases of sarcomatoid, 5 (10.8%) cases of biphasic, and 2 (4.3%) cases of desmoplastic subtype. ERβ expression was observed only in epithelioid (11 of total 36 cases) and biphasic (3 of total 5 cases) tumors. There was no significant difference in the incidence of ERβ expression in different subtypes of malignant pleural mesothelioma. Statistical analysis shows a significant difference in the expression of ERβ in the epithelioid subtype (with a more favorable prognosis) versus non-epithelioid subtypes (with poor prognosis, including sarcomatoid, desmoplastic, and biphasic) (P = 0.024). Discussion and Conclusion: Considering the higher proportion of the epithelioid type of MPM with ERβ expression, this highlights the role of ERβ in target therapy of MPM tumor, especially in the epithelioid subtype with a more favorable prognosis. A better understanding of the pathology of mesothelioma will eventually contribute to the development of therapies beyond the existing therapeutic platform.

Novel Therapeutic Targets and Immune Dysfunction in Malignant Pleural Mesothelioma

Advances in the treatment of malignant pleural mesothelioma (MPM) have been disappointing, despite the apparent need for new therapeutic options for this rare and devastating cancer. Drug resistance is common and surgical intervention has brought benefits only to a subset of patients. MPM is a heterogenous disease with a surprisingly low mutation rate and recent sequencing efforts have confirmed alterations in a limited number of tumor suppressors that do not provide apparent insights into the molecular mechanisms that drive this malignancy. There is increasing evidence that epigenetic regulation leads to immune evasion and transformation in MPM. Further, the low efficacy of immune checkpoint inhibitors is consistent with a suppression of genes involved in the anti-tumor immune response. We review three promising emerging therapeutic targets (STAT3, KDM4A, heparanase) and highlight their potential effects on the immune response.

New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.