{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:49:47Z","timestamp":1788306587668,"version":"build-2803163510"},"reference-count":26,"publisher":"Cold Spring Harbor Laboratory","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR) pathway, is currently approved for treatment of advanced renal-cell carcinoma (RCC) after failure of initial treatment with the tyrosine kinase inhibitors. Patients with tuberous sclerosis complex (TSC) syndrome can also develop RCC primarily mediated through mTOR signaling. However, the efficacy and duration of response of mTOR inhibition in patients with TSC-associated RCC is not well known. Herein, we describe a case of a patient with<jats:italic>TSC2<\/jats:italic>-associated metastatic RCC with mutations<jats:italic>H1620R<\/jats:italic>and<jats:italic>Y1650C<\/jats:italic>who has had an exceptional response to everolimus in the frontline setting and continues to derive benefit from mTOR inhibition 2 yr into therapy. Furthermore, the alteration<jats:italic>H1620R<\/jats:italic>in exon 37 resulting in a missense mutation is likely deleterious given our findings and previous analyses of the<jats:italic>TSC2<\/jats:italic>gene. Further studies of somatic mutations in extended responders to mTOR inhibitors will help personalize therapy for these patients. It also emphasizes the value of targeted therapies based on genomic analyses.<\/jats:p>","DOI":"10.1101\/mcs.a002220","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T13:45:21Z","timestamp":1522676721000},"page":"a002220","source":"Crossref","is-referenced-by-count":21,"title":["Exceptional response to everolimus in a novel tuberous sclerosis complex-2 mutation\u2013associated metastatic renal-cell carcinoma"],"prefix":"10.1101","volume":"4","author":[{"given":"Samer","family":"Alsidawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-7085","authenticated-orcid":false,"given":"Pashtoon Murtaza","family":"Kasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2018,4,2]]},"reference":[{"key":"2021112406070425000_4.2.a002220.1","doi-asserted-by":"publisher","DOI":"10.1086\/301705"},{"key":"2021112406070425000_4.2.a002220.2","doi-asserted-by":"publisher","DOI":"10.1086\/302648"},{"key":"2021112406070425000_4.2.a002220.3","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"2021112406070425000_4.2.a002220.4","first-page":"1201","article-title":"Tuberous sclerosis\u2013associated renal cell carcinoma. 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Tuberous sclerosis complex: genes, clinical features and therapeutics. 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Causes of death in patients with tuberous sclerosis. In Mayo Clinic Proceedings. 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