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MMT has been proposed as a therapeutic target for peritoneal metastasis. Most ovarian cancer (OC) patients present at diagnosis with peritoneal seeding, which makes tumor progression control difficult by MMT modulation. An alternative approach is to use antibody\u2013drug conjugates (ADCs) targeted directly to attack CAMs. This strategy could represent the cornerstone of precision\u2010based medicine for peritoneal carcinomatosis. Here, we performed complete transcriptome analyses of ascitic fluid\u2010isolated CAMs in advanced OC patients with primary\u2010, high\u2010, and low\u2010grade, serous subtypes and following neoadjuvant chemotherapy. Our findings suggest that both cancer biological aggressiveness and chemotherapy\u2010induced tumor mass reduction reflect the MMT\u2010associated changes that take place in the tumor surrounding microenvironment. Accordingly, MMT\u2010related genes, including fibroblast activation protein (<jats:italic>FAP<\/jats:italic>), mannose receptor C type 2 (<jats:italic>MRC2<\/jats:italic>), interleukin\u201011 receptor alpha (<jats:italic>IL11RA<\/jats:italic>), myristoylated alanine\u2010rich C\u2010kinase substrate (<jats:italic>MARCKS<\/jats:italic>), and sulfatase\u20101 (<jats:italic>SULF1<\/jats:italic>), were identified as specific actionable targets in CAMs of OC patients, which is a crucial step in the <jats:italic>de novo<\/jats:italic> design of ADCs. These cell surface target receptors were also validated in peritoneal CAMs of colorectal cancer peritoneal implants, indicating that ADC\u2010based treatment could extend to other abdominal tumors that show peritoneal colonization. As proof of concept, a FAP\u2010targeted ADC reduced tumor growth in an OC xenograft mouse model with peritoneal metastasis\u2010associated fibroblasts. In summary, we propose MMT as a potential source of ADC\u2010based therapeutic targets for peritoneal carcinomatosis. \u00a9 2023 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6170","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T04:56:13Z","timestamp":1691556973000},"page":"238-251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting carcinoma\u2010associated mesothelial cells with antibody\u2013drug conjugates in ovarian carcinomatosis"],"prefix":"10.1002","volume":"261","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7270-1629","authenticated-orcid":false,"given":"Luc\u00eda","family":"Pascual\u2010Ant\u00f3n","sequence":"first","affiliation":[{"name":"Tissue and Organ Homeostasis Program Centro de 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