title: Successful imatinib therapy for neuroendocrine carcinoma with activating Kit mutation: a case study.
abstract: Neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are believed to originate from the cells of Cajal that are randomly dispersed along the aerodigestive tract. Despite their distinct morphologic appearance, NET and GIST may share oncogenic mechanisms. Often presenting in the metastatic setting, treatment options for patients with NET are limited. This case report presents a patient with refractory metastatic NET that did not respond conventional chemotherapy. The patient was treated with a KIF11 inhibitor in a phase I clinical trial and experienced a prolonged and clinically meaningful partial response. On progression at 20 months, the patient's tumor was sequenced to reveal a KIT exon 11 mutation. Institution of imatinib therapy achieved a rapid and sustained antitumor effect with profound clinical benefit. Despite previously reported KIT expression in NET, this is the first documented case of an activating KIT mutation in NET and of successful treatment with both a KIF11 inhibitor and imatinib, each of which was elucidated through molecular profiling of the patient's tumor. Imatinib may be a valuable therapy in NET harboring activating KIT mutations.
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Perkins
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Patrick
authors.initials: P
authors.lastname: Boland
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Olszanski
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Paul
authors.initials: P
authors.lastname: Engstrom
authors.affiliation: From the Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute, Buffalo, New York; and Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Igor
authors.initials: I
authors.lastname: Astsaturov
mesh_terms: D001549:Benzamides / Q000008:administration & dosage*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D016547:Kinesins / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage*; D015398:Signal Transduction
chemical_list: D001549:Benzamides; C470243:KIF11 protein, human; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D016547:Kinesins