{"entity":{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","aka":[],"tldr":"An asbestos-caused cancer of the lung lining. Immunotherapy doublets replaced chemotherapy in 2020, and mesothelin CAR-T is under study.","summary":"Malignant pleural mesothelioma arises from the lining of the lung, almost always decades after asbestos exposure, and is rising in countries that banned asbestos late or not at all. It grows along surfaces rather than as a mass, is hard to image and stage, and resists most systemic therapy. Histology is the dominant biological variable: epithelioid tumours are slower and chemosensitive; sarcomatoid and biphasic tumours are aggressive, chemoresistant, and paradoxically more immunotherapy-responsive.\n\nFor 16 years after pemetrexed-cisplatin (2004) nothing improved survival except, modestly, adding bevacizumab (MAPS, 2016). Immunotherapy then changed the first line twice: nivolumab-ipilimumab (CheckMate 743, approved 2020) and pembrolizumab with chemotherapy (IND.227/KEYNOTE-483, approved September 2024). Tumour treating fields hold a device approval on single-arm data. Radical surgery, long assumed beneficial, was shown by MARS 2 (2024) to shorten survival and worsen quality of life, and is now largely confined to trials.\n\nWhat comes next is biology-led: PRMT5 and MAT2A inhibitors for the ~40-50% of tumours with MTAP deletion, mesothelin-directed CAR-T delivered into the pleural space, ADCs and T-cell engagers against mesothelin, and better use of histology and BAP1/CDKN2A status to choose therapy. Prevention remains the biggest lever: asbestos is still mined and used in parts of Asia, Russia, and Brazil.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Mesothelioma","links":[{"label":"NCI PDQ: malignant mesothelioma treatment","url":"https://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq"},{"label":"NICE NG12: suspected cancer, recommendations by site (lung and pleural cancers 1.1.1 to 1.1.6)","url":"https://www.nice.org.uk/guidance/ng12/chapter/Recommendations-organised-by-site-of-cancer"}],"tags":["thoracic"],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","car-t","ttfields","synthetic-lethality-approaches","pleurectomy-decortication","hipec","histopathology-ihc","antiangiogenic"],"targets":["mesothelin","pd1","ctla4","pdl1","vegf"],"drugs":["talc-sclerosant"],"companies":["orion-orion-pharma","bms","merck","novocure","boehringer-ingelheim"],"institutions":["mskcc","royal-marsden","the-christie","nki"],"pathways":["pd1-checkpoint","vegf-angiogenesis","p53-cell-cycle"],"terms":["epithelioid-vs-sarcomatoid","synthetic-lethality","irae","asbestos","tnm-9-lung-cancer"],"trials":["nct06097728"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Why mesothelioma is not a lung cancer. It arises from the mesothelial lining of the pleura rather than from the lung, the WHO classification gives it its own chapter, the IASLC runs a separate staging project for it whose ninth-edition proposals differ from the lung ones, and NICE NG12 gives it its own referral rules, lowering the threshold for an urgent chest X-ray in anyone aged 40 and over with a single unexplained respiratory symptom and a history of asbestos exposure. It shares the organ drawing with lung cancer because the drawing is anatomy, not taxonomy, and it shares asbestos as a cause; it is not a subtype of lung cancer on this site and is not listed as one."],"group":"thoracic","burden":"Mesothelioma causes about 30,000 cases a year worldwide, ~3,000 in the US, almost all from asbestos exposure 20-50 years earlier, so incidence is still rising in Asia and parts of Europe. Immunotherapy has produced the first tail of long-term survivors: in CheckMate 743 five-year survival was 14% against 6% with chemotherapy. Median survival across series is 12-18 months, which means half of the people in those series lived longer.","subtypes":["Epithelioid (~60-70%)","Biphasic (~20%)","Sarcomatoid (~10-20%, includes desmoplastic)","Peritoneal mesothelioma (~10-15% of all mesothelioma; treated with cytoreductive surgery and HIPEC)","Pericardial and testicular (rare)"],"biomarkers":["Histology (epithelioid vs sarcomatoid)","BAP1","CDKN2A/MTAP deletion","Mesothelin","Histology (epithelioid vs non-epithelioid) drives first-line choice","BAP1 loss (diagnostic; germline BAP1 syndrome)","CDKN2A/MTAP deletion (diagnostic; PRMT5-inhibitor target)","Mesothelin (CAR-T, ADC, engager target)","PD-L1 (weakly predictive)","Soluble mesothelin-related peptides and fibulin-3 (research)","Asbestos exposure history"],"standardOfCare":[{"setting":"Unresectable","approach":"Nivolumab-ipilimumab or chemo-IO; TTFields.","refs":["nivolumab","ipilimumab","pembrolizumab","optune"],"guideline":{"version":"NCCN Guidelines: Mesothelioma (Pleural)","url":"https://www.nccn.org/guidelines/category_1"}},{"setting":"Diagnosis and staging","approach":"CT and PET/CT; thoracoscopic biopsy with IHC panel (calretinin, WT1, D2-40; BAP1 and MTAP loss support malignancy); histology and BAP1/MTAP status recorded for treatment planning.","refs":["histopathology-ihc","pet-ct","ct"],"guideline":{"nccn":"MPM guideline","version":"NCCN Mesothelioma: Pleural v1.2026"}},{"setting":"First line, non-epithelioid","approach":"Nivolumab + ipilimumab (CheckMate 743) preferred; pembrolizumab + platinum-pemetrexed alternative.","refs":["nivolumab","ipilimumab","checkmate-743","pembrolizumab","keynote-483","histology-directs-first-line-meso"],"guideline":{"nccn":"1 (preferred)","esmoMcbs":"4"}},{"setting":"First line, epithelioid","approach":"Pembrolizumab + platinum-pemetrexed, nivolumab + ipilimumab, or platinum-pemetrexed ± bevacizumab, chosen by fitness and preference.","refs":["pembrolizumab","keynote-483","nivolumab","ipilimumab","pemetrexed","maps"],"guideline":{"nccn":"1 (chemo-IO and IO doublet); 2A (bevacizumab)","esmoMcbs":"3"}},{"setting":"Maintenance","approach":"Continue immunotherapy per regimen; TTFields (Optune Lua) with pemetrexed-platinum under HDE approval; no maintenance chemotherapy standard.","refs":["optune","ttfields","stellar"],"guideline":{"nccn":"2B (TTFields)"}},{"setting":"Second line","approach":"Nivolumab (CONFIRM: OS benefit vs placebo) or nivolumab-ipilimumab if not given first line; platinum-pemetrexed rechallenge or gemcitabine/vinorelbine if IO given first; trials.","refs":["nivolumab","pemetrexed"],"guideline":{"nccn":"2A"}},{"setting":"Surgery","approach":"Not recommended for cure outside trials after MARS 2; VATS pleurodesis or indwelling pleural catheter for effusion; extended pleurectomy/decortication (P/D) only in clinical trials.","refs":["pleurectomy-decortication","mars-2"],"guideline":{"nccn":"Selected centres/trials only"}},{"setting":"Radiotherapy","approach":"Palliative for chest wall pain; prophylactic tract irradiation not beneficial (SMART/PIT trials); hemithoracic IMRT after surgery only in trials.","refs":["imrt-igrt"]},{"setting":"Peritoneal mesothelioma","approach":"Cytoreductive surgery with HIPEC in selected patients; systemic therapy extrapolated from pleural disease.","refs":["hipec"]}],"stateOfArt":["IO doublet first line.","Two immunotherapy-based first-line standards (nivolumab-ipilimumab; pembrolizumab-chemotherapy), chosen by histology.","Radical surgery removed from routine care after MARS 2 showed harm.","Five-year survival with nivolumab-ipilimumab 14% vs 6% with chemotherapy: a small but real tail of long-term survivors.","MTAP deletion and BAP1 loss are routine diagnostic markers and emerging therapeutic handles.","Mesothelin CAR-T delivered regionally has produced long survivors in phase 1."],"history":[{"year":1960,"title":"Wagner links mesothelioma to asbestos in South African miners","refs":[]},{"year":1989,"title":"US EPA asbestos ban partly overturned (1991); many countries ban asbestos over the following decades","refs":[]},{"year":2003,"title":"EMPHACIS: pemetrexed-cisplatin improves survival","refs":["pemetrexed"]},{"year":2004,"title":"Pemetrexed-cisplatin approved","refs":[]},{"year":2004,"title":"Pemetrexed approved: first mesothelioma drug","refs":["pemetrexed"]},{"year":2011,"title":"MARS 1: extrapleural pneumonectomy shows harm; practice shifts to lung-sparing surgery","refs":["pleurectomy-decortication"]},{"year":2016,"title":"MAPS: bevacizumab adds ~3 months","refs":["maps"]},{"year":2019,"title":"TTFields device approval (HDE) on STELLAR","refs":["stellar","optune"]},{"year":2019,"title":"LUME-Meso fails; nintedanib abandoned in mesothelioma","refs":["lume-meso","nintedanib"]},{"year":2020,"title":"Nivolumab-ipilimumab first line","refs":[]},{"year":2020,"title":"CheckMate 743: nivolumab-ipilimumab approved, first new first line in 16 years","refs":["checkmate-743","nivolumab","ipilimumab"]},{"year":2021,"title":"CONFIRM: nivolumab improves survival in relapsed disease","refs":["nivolumab"]},{"year":2023,"title":"IND.227/KEYNOTE-483 positive for pembrolizumab-chemotherapy","refs":["keynote-483"]},{"year":2024,"title":"MARS 2: surgery worsens survival; pembrolizumab-chemotherapy approved (September)","refs":["mars-2","pembrolizumab"]},{"year":2024,"title":"BEAT-meso misses OS; non-epithelioid subgroup benefits","refs":["beat-meso"]},{"year":2025,"title":"CheckMate 743 five-year data: 14% vs 6% alive","refs":["checkmate-743"]},{"year":2026,"title":"DREAM3R stopped early; PRMT5 inhibitors and mesothelin cell therapies advance","refs":["dream3r","idea-mtap-prmt5-mesothelioma","idea-mesothelin-car-t-regional"]}],"pipeline":["synthetic-lethality-approaches","eb-mf-car-nk-01","anetumab-ravtansine","idea-adc-for-mesothelioma","anetumab-vs-vinorelbine-mpm","nci-anetumab-pembrolizumab-mpm","ucl-proton-hemithoracic-mpm","proton-therapy","idea-mtap-prmt5-mesothelioma","idea-mesothelin-car-t-regional","car-t","armored-car","mesothelin","t-cell-engager","adc","checkpoint-inhibitor","ttfields","histology-directs-first-line-meso","fapi-pet"],"openProblems":["Sarcomatoid subtype.","No early detection despite known exposure.","Even the best first-line regimens give a median survival under two years; the tail of long survivors on immunotherapy is what to build on.","Epithelioid disease gains little from immunotherapy over chemotherapy; no predictive biomarker beyond histology.","No approved targeted therapy despite recurrent BAP1, CDKN2A/MTAP, and NF2 alterations.","Once immunotherapy has been used first line, the second-line options are platinum-pemetrexed rechallenge, gemcitabine or vinorelbine, none with a randomised survival trial behind it in that sequence; mesothelin CAR-T, mesothelin ADCs and engagers, and PRMT5 inhibitors for MTAP-deleted tumours are the trials addressing it.","Surgery's role is now unclear for the small group of early, epithelioid, node-negative patients.","Response assessment is hard (modified RECIST for pleural rind); trials are small and slow.","Asbestos is still produced and used in several large countries; incidence will rise there for decades.","Peritoneal and rarer sites lack dedicated evidence."]},"route":"/cancers/mesothelioma/","neighbours":{"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"rejuv-rehab-respiratory","kind":"technology","name":"Breathing and exercise capacity after lung resection","route":"/technologies/rejuv-rehab-respiratory/"},{"id":"stroma-directed-car","kind":"technology","name":"CAR-T against stroma: fibroblasts and myeloid cells","route":"/technologies/stroma-directed-car/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"id":"rejuv-measure-eortc-qlq-c30","kind":"technology","name":"EORTC QLQ-C30: the questionnaire most cancer trials use","route":"/technologies/rejuv-measure-eortc-qlq-c30/"},{"id":"pleurectomy-decortication","kind":"technology","name":"Extended pleurectomy/decortication & radical mesothelioma surgery","route":"/technologies/pleurectomy-decortication/"},{"id":"fapi-pet","kind":"technology","name":"FAPI PET","route":"/technologies/fapi-pet/"},{"id":"hipec","kind":"technology","name":"HIPEC / PIPAC (intraperitoneal chemotherapy)","route":"/technologies/hipec/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"metabolic-therapy","kind":"technology","name":"Metabolic therapy: starving the tumour of a nutrient","route":"/technologies/metabolic-therapy/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"},{"id":"ttfields","kind":"technology","name":"Tumour treating fields (TTFields)","route":"/technologies/ttfields/"},{"id":"rejuv-measure-minimally-important-difference","kind":"technology","name":"What a difference has to be before a person would notice it","route":"/technologies/rejuv-measure-minimally-important-difference/"}],"target":[{"id":"arhgap5","kind":"target","name":"ARHGAP5","route":"/targets/arhgap5/"},{"id":"bap1","kind":"target","name":"BAP1","route":"/targets/bap1/"},{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"cyp2c8","kind":"target","name":"CYP2C8","route":"/targets/cyp2c8/"},{"id":"ddx3x","kind":"target","name":"DDX3X","route":"/targets/ddx3x/"},{"id":"dgcr8","kind":"target","name":"DGCR8","route":"/targets/dgcr8/"},{"id":"ercc1","kind":"target","name":"ERCC1","route":"/targets/ercc1/"},{"id":"fat4","kind":"target","name":"FAT4","route":"/targets/fat4/"},{"id":"flg","kind":"target","name":"FLG","route":"/targets/flg/"},{"id":"gart","kind":"target","name":"GART (trifunctional purine synthesis 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(MTAP-deleted cancers)","route":"/targets/prmt5-mtap/"},{"id":"ptprb","kind":"target","name":"PTPRB","route":"/targets/ptprb/"},{"id":"rhoa","kind":"target","name":"RHOA","route":"/targets/rhoa/"},{"id":"setd2","kind":"target","name":"SETD2","route":"/targets/setd2/"},{"id":"setdb1","kind":"target","name":"SETDB1","route":"/targets/setdb1/"},{"id":"shtn1","kind":"target","name":"SHTN1","route":"/targets/shtn1/"},{"id":"srgap3","kind":"target","name":"SRGAP3","route":"/targets/srgap3/"},{"id":"taf15","kind":"target","name":"TAF15","route":"/targets/taf15/"},{"id":"tbl1xr1","kind":"target","name":"TBL1XR1","route":"/targets/tbl1xr1/"},{"id":"traf7","kind":"target","name":"TRAF7","route":"/targets/traf7/"},{"id":"vegf","kind":"target","name":"VEGF / VEGFR","route":"/targets/vegf/"},{"id":"vista","kind":"target","name":"VISTA","route":"/targets/vista/"},{"id":"wnk2","kind":"target","name":"WNK2","route":"/targets/wnk2/"},{"id":"wt1","kind":"target","name":"WT1","route":"/targets/wt1/"}],"drug":[{"id":"anetumab-ravtansine","kind":"drug","name":"Anetumab ravtansine","route":"/drugs/anetumab-ravtansine/"},{"id":"eb-mf-car-nk-01","kind":"drug","name":"EB-MF-CAR-NK-01","route":"/drugs/eb-mf-car-nk-01/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nintedanib","kind":"drug","name":"Nintedanib","route":"/drugs/nintedanib/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"optune","kind":"drug","name":"Optune / Optune Pax 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