{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:39:07Z","timestamp":1792726747933,"version":"4.5.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,1,26]]},"abstract":"<jats:p>\n                    Most genetically engineered mouse (GEM) models for colon cancer are based on tissuewide or germline gene modification, resulting in tumors predominantly of the small intestine. Several of these models involve modification of the adenomatous polyposis coli (\n                    <jats:italic>Apc<\/jats:italic>\n                    ) gene and are excellent models for familial cancer predisposition syndromes. We have developed a stochastic somatic mutation model for sporadic colon cancer that presents with isolated primary tumors in the distal colon and recapitulates the entire adenoma\u2013carcinoma\u2013metastasis axis seen in human colon cancer. Using this model, we have analyzed tumors that are either solely mutant in the\n                    <jats:italic>Apc<\/jats:italic>\n                    gene or in combination with another colon cancer-associated mutant gene, the\n                    <jats:italic>Kras<\/jats:italic>\n                    G12D allele. Because of the restricted location in the distal colon, the natural history of the tumors can be analyzed by serial colonoscopy. As the mammalian target of rapamycin (mTOR) pathway is a critical component of the complex signaling network in colon cancer, we used this model to assess the efficacy of mTOR blockade through rapamycin treatment of mice with established tumors. After treatment,\n                    <jats:italic>Apc<\/jats:italic>\n                    mutant tumors were more than 80% smaller than control tumors. However, tumors that possessed both\n                    <jats:italic>Apc<\/jats:italic>\n                    and\n                    <jats:italic>Kras<\/jats:italic>\n                    mutations did not respond to rapamycin treatment. These studies suggest that mTOR inhibitors should be further explored as potential colorectal cancer therapies in patients whose tumors do not have activating mutations in KRAS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0908682107","type":"journal-article","created":{"date-parts":[[2010,1,4]],"date-time":"2010-01-04T21:36:36Z","timestamp":1262640996000},"page":"1565-1570","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":178,"title":["Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment"],"prefix":"10.1073","volume":"107","author":[{"given":"Kenneth E.","family":"Hung","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Tufts Medical Center, Boston, MA 02111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Maricevich","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Georgeon","family":"Richard","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School and Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tufts Medical Center, Boston, MA 02111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Tufts Medical Center, Boston, MA 02111;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kunin","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick T.","family":"Bronson","sequence":"additional","affiliation":[{"name":"Dana Farber\/Harvard Cancer Center, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Kucherlapati","sequence":"additional","affiliation":[{"name":"Department of Genetics, Harvard Medical School and Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,1,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/CA.2007.0010"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2110"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2192"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.049"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81333-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc777"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.943001"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204837"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2123"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404761101"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.02.016"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1173"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.120"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2441052114"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1674008"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020146"},{"key":"e_1_3_3_17_2","first-page":"1999","article-title":"Somatic mutational mechanisms involved in intestinal tumor formation in Min mice","volume":"57","author":"Shoemaker AR","year":"1997","unstructured":"AR Shoemaker, C Luongo, AR Moser, LJ Marton, WF Dove, Somatic mutational mechanisms involved in intestinal tumor formation in Min mice. 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