{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:58Z","timestamp":1792790338547,"version":"4.5.0"},"posted":{"date-parts":[[2026,3,26]]},"group-title":"Cancer Biology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"United States Army Medical Research and Development Command","id":[{"id":"https:\/\/ror.org\/03cd02q50","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Children\u2019s Tumor Foundation","id":[{"id":"https:\/\/ror.org\/01hx92781","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Schwannomas are debilitating hallmarks of familial schwannomatoses and common sporadic tumors that form on spinal and cranial nerves. Drug-based therapies for schwannoma are desperately needed but their development has been extremely slow and disappointing, impeded particularly by the poorly understood and surprisingly complex and heterogeneous biology of schwannomas, and by the inefficient use of physiologically relevant\n                  <jats:italic>in vivo<\/jats:italic>\n                  preclinical models. We have addressed these gaps by developing a quantitative imaging-centered workflow that allows both a deep analysis of schwannoma development and accelerated preclinical testing in a widely used genetically engineered mouse model of neurofibromatosis type 2-related schwannomatosis (\n                  <jats:italic>NF2<\/jats:italic>\n                  -SWN). We deployed our workflow to study schwannoma development and to test three clinically relevant drugs head-to-head. Our results uncovered the very early onset of heterogeneity and macrophage recruitment to initiating schwannomas and unexpectedly revealed that although all three drugs inhibited proliferation within the developing schwannomas, they did so while triggering one of two distinct response signatures, highlighting the value of our pipeline for both rapid drug-testing and translational discovery.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Schwannomas are common sporadic tumors that grow on cranial and spinal nerves, as well as defining features of familial schwannomatosis. Therapeutic advance has been hampered by the striking heterogeneity of schwannomas, Schwann cell plasticity, and the poorly understood biology of interactions between tumor cells and the microenvironment. To address this gap, we exploited a widely used mouse model of schwannomatosis to develop a quantitative imaging platform that captures diverse tumor features, including proliferation, biomarkers of heterogeneity, and macrophage recruitment. We deployed this workflow to holistically compare three clinically active drugs head-to-head and discovered that despite similarly inhibiting proliferation, the drugs induced two distinct response signatures, underscoring the value of this pipeline for accelerated preclinical testing and discovery-based studies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.24.714069","type":"posted-content","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T04:56:04Z","timestamp":1774587364000},"source":"Crossref","is-referenced-by-count":0,"title":["Quantitative imaging of schwannoma captures heterogeneity and accelerates preclinical testing, exposing distinct therapeutic signatures"],"prefix":"10.64898","author":[{"given":"Emily A.","family":"Wright","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA"},{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street Boston, MA 02114 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-7988","authenticated-orcid":false,"given":"Jeremie","family":"Vitte","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA and Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles, Los Angeles, CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9378-9148","authenticated-orcid":false,"given":"Sara I.","family":"Veiga","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA 02114 USA"},{"name":"The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Bushnell","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA"},{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street Boston, MA 02114 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Movsessian","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA"},{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street Boston, MA 02114 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA"},{"name":"Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street Boston, MA 02114 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Curtis","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8173-5778","authenticated-orcid":false,"given":"Ryan B.","family":"Corcoran","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Krantz Family Center for Cancer Research, Harvard 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