Supportive Care For Pleural Mesothelioma Patients: Resources – Pharmacological targeting of MMP2/9 reduces colorectal cancer peritoneal metastases in a human ex vivo peritoneal culture model.

Trimodality, a four-step treatment including chemotherapy, pleurectomy/decortication, and radiotherapy in early-stage malignant pleural mesothelioma: a single-institution retrospective case study

Supportive Care For Pleural Mesothelioma Patients: Resources

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Pdf) Treatment Patterns Among Patients With Malignant Pleural Mesothelioma: An Italian, Population‐based Nationwide Study

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What Is Mesothelioma? Overview Of Types, Symptoms & Treatment

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By Yanyun Gao Yanyun Gao Scilit Preprints.org Google Scholar 1, 2 , Marianna Kruithof-de Julio Marianna Kruithof-de Julio Scilit Preprints.org Google Scholar 3, 4, 5 , Ren-Wang Peng Ren-Wang Peng Scilit Google Preprints.org Scholar 1, 2, * and Patrick Dorn Patrick Dorn Scilit Preprints.org Google Scholar 1, 2, *

Received: 22 June 2022 / Revised: 26 July 2022 / Accepted: 29 July 2022 / Published: 2 August 2022

Mesothelioma: Causes, Symptoms, And More

Malignant pleural mesothelioma (MPM) is a highly lethal cancer, known for its limited treatment options, lack of targeted therapies, and disastrous survival rates. MPM tumors are highly heterogeneous and show significant variation in the genomic landscape among individual patients, characterized by widespread loss-of-function mutations of tumor suppressor genes (TSGs) that are difficult to target. Therefore, there is an urgent and unmet need for new therapeutic targets and strategies for personalized treatment. Patient-derived organoids (PDOs), next-generation tumor models that have significantly influenced the discovery of anticancer drugs and biomarkers of treatment response in many other cancers, are emerging and promise to play a key role in understanding the biology of MPM. Importantly, in identifying and developing appropriate oncology approaches tailored to specific subsets of patients with MPM.

MPM is an aggressive tumor arising from pleural mesothelial cells. A characteristic feature of the disease is the predominant distribution of therapeutically inactivating mutations in TSGs, which makes MPM one of the most difficult cancers to treat and a type of cancer characterized by a significant lack of treatment options and an extremely poor prognosis (5 – year survival rate only 5% to 10%). Extensive intra-disease heterogeneity represents another major challenge for targeted MPM therapy, warranting stratified therapy for specific subgroups of MPM patients. Accurate preclinical models are critical for new drug discovery and personalized medicine development. Organoids, an in vitro ‘organ-like’ construct derived from a patient’s tumor tissue that faithfully mimics the complex biology and architecture of cancer and overcomes many of the shortcomings of other existing models, is a next-generation tumor model. Although organoids have been successfully produced and used in many types of cancer, the development of MPM organoids is still in its infancy. Here, we provide an overview of recent developments in the field of cancer organoids, focusing on the advances and challenges in the development of MPM organoids. We also detail the potential of MPM organoids to understand the pathobiology of MPM, discover new therapeutic targets and develop personalized therapies for MPM patients.

Malignant mesothelioma is a rare but aggressive type of cancer that arises from the mesothelium (outer serous lining) of the pleura, pericardium, peritoneum, and tunica vaginalis that covers the lungs, heart, stomach, and testes. Malignant pleural mesothelioma (MPM) accounts for 90% of all mesotheliomas, and the 5-year survival rate remains 5% to 10% [1]. Asbestos exposure is the most common cause of MPM with a latency period of 20 to 50 years [2]. Asbestiform fibers (erionite, vinhite, magnesium-ribekit, richterite, Libby asbestos, antigorite and fluor-edenite) are causally associated with MPM [3]. Histologically, MPM is divided into four subtypes: epithelioid (50-60%), sarcomatoid (10%), biphasic (30-40%) and desmoplastic (<2%) [4], with the epithelioid subtype having associated with better survival. compared to other subtypes [1, 5]. Molecularly, MPM is characterized by frequent mutations in TSGs, including BAP1, CDKN2A, and NF2, while driver mutations in oncogenes are rare, leading to the development of targeted therapies against MPM. [6, 7, 8] raises an important issue. Platinum-based doublet chemotherapy has been the standard first-line treatment for advanced MPM since 2003 [9] , with an effective second-line treatment for inevitable drug resistance still elusive [10] . Immunotherapy (eg, immune checkpoint inhibitors, ICIs) has recently been approved as a new first-line treatment for intractable MPM [11] due to beneficial patient benefit compared to chemotherapy in clinical trials [11, 12]. Therefore, new therapeutic targets and strategies are urgently needed for the effective treatment of MPM [ 13 , 14 , 15 , 16 ]. Recent evidence reveals that MPM tumors are highly heterogeneous, making one-size-fits-all strategies difficult [ 17 , 18 , 19 , 20 ] and instead emphasizing individualized oncology-based care of MPM patients.

Mesothelioma And Covid 19: Don’t Skip Screening And Treatment

Accurate preclinical models that faithfully capture the genomic and histopathological features of MPM are critical for accurate identification and drug development [ 21 ]. Two-dimensional (2D) culture of MPM cell lines, established from primary tumors or pleural fluid [22], are the most commonly used models, but have important limitations, such as the lack of tissue architecture and the complexity of biological processes in vivo. [23]. ]. Animal models of MPM have also been established, including asbestosis-induced mouse tumors, genetically modified MPM mice, and patient-derived xenograft (PDX) models [ 24 , 25 , 26 ]. While 2D culture and mouse models are useful, patient-derived organoids (PDO), an in vitro culture of a three-dimensional (3D) organ structure that faithfully mimics the complex biology and architecture of primary cancer, represents a new generation tumor. model with clear advantages over other existing models [27]. Organoids have been successfully established in colon, gastrointestinal, pancreatic, prostate, liver, and brain cancers, but efforts to develop MPM organoids are still a largely unsuccessful endeavor [ 28 , 29 , 30 ]. In this review, we present the recent developments in PDO, with a focus on the progress and challenges in the development of MPM organoids. We also discuss how MPM organoids will revolutionize our understanding of MPM pathobiology at the molecular level, facilitate the discovery of new therapeutic targets and strategies, and accelerate the development of truly personalized medicine for MPM patients.

The term ‘organoid’ refers to mini-groups of cells that organize and differentiate into functional cell types in vitro and describe the structure and function of organs in vivo (hence the name “mini-organs”) [ 31]. Organoid culture dates back to 1907, when H. V. Wilson first reported that sponge cells could self-organize to regenerate an entire organism in vitro [ 31 , 32 ]. A few decades later, researchers conducted isolation and harvesting experiments to produce various organs from embryonic stem cells in the veins [ 31 , 33 ]. With the development of stem cell research, such as the isolation of pluripotent stem cells (PSCs) and the generation of induced PSCs (iPSCs), organoid research has greatly advanced in the late 20th and early 21st centuries, as organoids can to be made of PSCs. embryonic and adult stem cells) and iPSCs [34, 35, 36]. In 2009, adult intestinal stem cells expressing single leucine-rich G protein-coupled receptor 5 (Lgr5) formed 3D intestinal organoids in Matrigel that self-organized and crypto-villus structures without a mesenchymal trace; this was the first report of a 3D organoid culture derived from a single adult stem cell [37]. Since then, 3D organoid systems have attracted much attention and shown great potential for modeling human cancers [ 38 , 39 , 40 , 41 ]. To date, organoids have been used for many types of cancer, including colon cancer [42], gastrointestinal cancer [29], pancreatic cancer [43], prostate cancer [30, 44], bladder cancer [45, 46], and liver cancer. are also made in. [47], breast cancer [48] and brain cancer [49].

There is increasing interest in the development and use of patient-derived organs (PDOs) for cancer research. Along with this development, different methods and protocols of PDO extraction have been developed for different types of cancer.

A Survey Of Patient And Caregiver Experience With Malignant Pleural Mesothelioma

There are now several methods for producing PDO, including Matrigel-based culture, suspension culture, and culture on a chip. Most human cancer organoids can be produced using Matrigel, which is a hydrogel at 24–37 °C and a liquid at 0–4 °C. Specifically, single cells obtained from human tumor tissue are resuspended in Matrigel or organoid medium containing Matrigel [ 50 ]. Cultivation of organoids from different cancers varies in terms of tissue perfusion method, seeding cell density, Matrigel concentration, culture plate type, and culture medium. Recently, various biomaterials have been developed as substitutes

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