{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T23:27:36Z","timestamp":1786663656665,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,11]]},"group-title":"Cancer Biology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Meningiomas are the most common primary nervous system neoplasm in adults. There are few good cellular models, especially of high grade\/malignant meningiomas, to use to identify new therapeutic agents and treatment regimens. The widely available, partially characterized,\n                    <jats:italic>NF2-<\/jats:italic>\n                    wildtype (\n                    <jats:italic>NF2<\/jats:italic>\n                    wt) Grade 3 malignant meningioma cell line IOMM-Lee can help meet this need.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We generated new data to better characterize IOMM-Lee genomic and mtDNA variants, proliferation rate and colony-forming efficiency and sensitivity to ionizing radiation as a function of ATM kinase activity. A screen of 349 anti-cancer drugs identified multiple, mechanistically distinct clinical use drugs with nanomolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values and high drug sensitivity prediction scores.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Exome sequencing confirmed that IOMM-Lee is\n                    <jats:italic>NF2wt<\/jats:italic>\n                    , and contains a pathogenic\n                    <jats:italic>TERT<\/jats:italic>\n                    -promoter (c.-124C&gt;T) variant. Population doubling times (PDT) were short (19-21 hrs), and colony forming efficiency (CFE) high, of up to 87%. IOMM-Lee is comparatively radiosensitive with a D\n                    <jats:sub>10<\/jats:sub>\n                    of \u223c3.9 Gy, and could be radiosensitized by AZD-1390-mediated ATM kinase inhibition. Thirty-four anti-cancer compounds spanning several mechanistic classes were identified that potently suppressed cell proliferation at sub-micromolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values with high Breeze 2.0 Drug Sensitivity Scores.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Importance of the Study<\/jats:title>\n                  <jats:p>\n                    We provide new data to better characterize IOMM-Lee, the most widely used cell line model of human Grade 3 malignant meningioma. These data identify and characterize IOMM-Lee genomic alterations and mtDNA variants; quantify growth kinetics and ionizing radiation sensitivity; and identify multiple mechanistically distinct, clinical use drugs with nanomolar IC\n                    <jats:sub>50<\/jats:sub>\n                    values, high drug sensitivity prediction scores and potential as meningioma systemic therapies. Our data more clearly locate IOMM-Lee in the landscape of genomically-defined meningiomas, and will aid better use of this experimentally tractable cell line model to understand meningioma biology and identify more effective malignant meningioma therapies and treatment regimens.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>\n                        IOMM-Lee lacks\n                        <jats:italic>NF2<\/jats:italic>\n                        mutations, though is clearly related to but distinct from many other meningiomas and meningioma cell lines.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        IOMM-Lee grows rapidly, is comparatively radio-sensitive, and can be suppressed by several mechanistic classes of anti-cancer agents at clinically achievable, sub-micromolar IC\n                        <jats:sub>50<\/jats:sub>\n                        values with high Drug Sensitivity Scores.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        The experimental tractability, simplicity and versatility of IOMM-Lee can facilitate analyses of many aspects of meningioma biology and therapeutic development across a wide range of\n                        <jats:italic>in vitro<\/jats:italic>\n                        , high throughput and\n                        <jats:italic>in vivo<\/jats:italic>\n                        xenograft\/organoid protocols.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                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