Phytochemicals in Malignant Pleural Mesothelioma Treatment-Review on the Current Trends of Therapies.
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ABSTRACT:
SUBMITTER: Chmielewska-Kassassir M
PROVIDER: S-EPMC8348618 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mesothelioma is a highly lethal tumor derived from mesothelial cells, and its global incidence is increasing because of widespread exposure of numerous individuals to asbestos in the last 50 years. Mesothelioma is largely untreatable with any of the therapeutic modalities. Recently, a novel multitargeted antifolate pemetrexed has shown promising activity against malignant pleural mesothelioma, producing response rates of up to 40% when used in combination with cisplatin. In a large phase III study, use of a combination of pemetrexed and cisplatin was associated with significantly improved survival time and with greater antitumor activity compared with cisplatin alone. This combination also gave a significant response rate of approximately 50% in patients with epithelioid malignant pleural mesothelioma. These clinical benefits of pemetrexed-cisplatin doublet have changed the perception of mesothelioma chemotherapy. Other combinations, including gemcitabine in combination with cisplatin, have also shown encouraging response rates. Prognosis depends on gender, clinical stage of the tumor, histological subtype, platelet count, leukocyte counts, and performance status. Radiotherapy can palliate mesothelioma patients with chest pain, and has been indicated to be of benefit for the prevention of malignant seeding along the tract of a chest tube or needle biopsy. Trimodality treatment using extrapleural pneumonectomy, radiation and chemotherapy has shown promising therapeutic value. The development of chemotherapeutic regimens and the favorable outcomes of trimodality have led to new combined modality trials. In Japan, multicenter national trials against mesothelioma will begin in the near future.
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Project description:The incidence of malignant pleural mesothelioma is expected to increase globally. New treatment options for this malignancy are eagerly awaited to improve the survival and quality of life of patients. The present article highlights the results of recent advances in this field, analyzing data from several relevant trials. The heterogeneous tumor microenvironment and biology, together with the low mutational burden, pose a challenge for treating such tumors. So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.
| S-EPMC10741667 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a 5-year survival rate of ~10%. Since most patients present with irresectable disease, the vast majority is treated with chemotherapy. The only registered therapy for MPM is platinum-pemetrexed doublet therapy, although only up to half of patients have clinical benefit from this palliative treatment. Of the anti-angiogenesis agents, only bevacizumab and nintedanib have shown activity with platinum-pemetrexed doublet therapy. Other anti-angiogenesis agents like thalidomide did not prolong (progression free) survival or response rate. Eventually, all patients will get a recurrence and no active second line therapy has been identified to date. The clinical benefit of (switch) maintenance therapy after first line treatment and combination strategies of different chemotherapies with angiogenesis inhibitors are currently under investigation. The major challenges are finding optimal treatment combinations and to select the adequate treatment for an individual patient. This review focusses on the current standard of chemotherapy and new systemic therapy strategies under investigation.
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Project description:Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.
| S-EPMC6992646 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is a rare disease of the pleura and is largely related to asbestos exposure. Despite recent advancements in technologies and a greater understanding of the disease, the prognosis of MPM remains poor; the median overall survival rate is about 6 to 9 months in untreated patients. The main therapeutic strategies for MPM are surgery, chemotherapy, and radiation therapy (RT). The two main surgical approaches for MPM are extrapleural pneumonectomy (EPP), in which the lung is removed en bloc, and pleurectomy/decortication, in which the lung stays in situ. Chemotherapy usually consists of a platinum-based chemotherapy, such as cisplatin, often combined with a folate antimetabolite, such as pemetrexed. More recently, immunotherapy has emerged as a possible therapeutic strategy for MPM. Evidence suggests that single-modality treatments are not an effective therapeutic approach for MPM. Therefore, researchers have started to explore different multimodality treatment approaches, in which often combinations of surgery, chemotherapy, immunotherapy, and RT are investigated. There is still no definitive answer to the question of which multimodality treatment combinations are most effective in improving the poor prognosis of MPM. Research into the effects of trimodality treatment approaches have found that radical approaches such as EPP and hemithoracic RT post-EPP are less effective than was previously assumed. In general, there are still a great number of unanswered questions and unknown factors regarding the ideal treatment approach for MPM. Hopefully, more research into multimodality therapy will provide insight into which combination of treatment modalities is most effective.
| S-EPMC6198256 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical) pleurectomy (e-P/D) in selected patients and can result in prolonged survival when incorporated into a multimodality approach. Given the morbidity associated with surgical resection of MPM, optimizing identification of appropriate patients is essential. Unfortunately, most patients are not candidates for EPP or e-P/D due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum combination chemotherapy has become the cornerstone of therapy for patients with unresectable disease because the combination is associated with improved survival and quality of life in treated patients. However, MPM eventually becomes resistant to initial therapy, and benefit to further lines of therapy has not been substantiated in randomized clinical trials. Translational research has provided exciting insights into tumorigenesis, biomarkers, and immune response in MPM, leading to the development of multiple novel therapeutic agents that are currently in clinical trials. These advances hold the promise of a new era in the treatment of MPM and suggest that this disease will not be left behind in the war on cancer.
| S-EPMC4153452 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) has been marked historically by poor prognosis. Current standard of care for this deadly disease results in sub-optimal improvements in overall survival (OS), which has prompted researchers to explore innovative treatment alternatives. Immunotherapy is an emerging therapeutic modality that harnesses the power of the human immune system. In this review, we summarize the different methods of immunotherapy for malignant pleural mesothelioma. Using ClinicalTrials.gov we searched the terms "immunotherapy" and "immune therapy" combined with "pleural mesothelioma". Our search yielded 75 trials, among which 37 trials met our specific criteria. Our search identified immune checkpoint blockade, immunotoxin therapy, anticancer vaccines, oncolytic viral therapy, and adoptive cell therapy as the most common and pertinent methods of immunotherapy currently being assessed in clinical trials. We have reviewed the most up-to-date clinical trials involving immunotherapeutic approaches for the treatment of malignant pleural mesothelioma. In addition to highlighting some of the successes of immunotherapy, we also have identified limitations that must be overcome to improve the efficacy of these therapies.
| S-EPMC5504119 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease. Currently, the platinum doublet of pemetrexed and cisplatin is the standard first-line treatment for unresectable MPM. However, recent promising results of immunotherapy have markedly changed the landscape of MPM treatment. Further, the ongoing innovative therapeutic strategies are expected to expand the range of treatment options; however, several questions remain unanswered. First, establishing predictive biomarkers with high potency is urgently needed to optimize the patient selection process. Second, further exploration of the combination algorithm is expected to unveil more effective and safe regimens. Moreover, other dilemmas, such as the resistance mechanism of immunotherapy and the role of immunotherapy in perioperative settings, still warrant further exploration.
| S-EPMC9215716 | biostudies-literature
Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.
2005-06-01 | GSE2549 | GEO
Project description:Mesothelioma is a rare malignancy of the pleura with limited therapeutic options. Despite the desperate need to develop better treatment for this disease, the rarity of the tumor type creates formidable challenges in clinical research. Nonetheless, several novel agents are under investigation. Most efforts are directed toward improving standard first-line therapy with pemetrexed and cisplatin, or developing effective second-line treatments. Several classes of drugs are being explored, including those that impact DNA transcription, cell-cycle progression, angiogenesis, and immune tolerance. This article describes several ongoing or recently completed phase II and III trials using novel agents vorinostat, everolimus, CBP501, MORAb-009, NGR-hTNF, WT1 vaccine, bevacizumab, cediranib, and thalidomide.
| S-EPMC4343316 | biostudies-literature