知搜-全球专利检索

  1. 登录
  2. 注册

搜索结果

14 条记录 (耗时 0.018 秒)

    OVARIAN CARCINOMA DETECTION AND PROPHYLAXIS
    2.
    发明申请
    OVARIAN CARCINOMA DETECTION AND PROPHYLAXIS 审中-公开

    公开(公告)号：US20170327898A1

    公开(公告)日：2017-11-16

    申请号：US15596517

    申请日：2017-05-16

    申请人： THE JOHNS HOPKINS UNIVERSITY

    发明人： Victor Velculescu ,  Eniko Papp ,  Vilmos Adleff

    IPC分类号： C12Q1/68 ,  G06F19/00 ,  G06F19/18

    CPC分类号： C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/156 ,  G06F19/3481 ,  G16B10/00 ,  G16B20/00 ,  G16H50/30

    摘要： The evolutionary origin of high-grade serous ovarian carcinoma remains largely unknown. The vast majority of tumor-specific genomic alterations from ovarian cancers are present in fallopian tube STIC lesions (average of 55 sequence alterations per tumor), including those affecting TP53, BRCA1, BRCA2 or PTEN genes. A quantitative evolutionary analysis indicated that tumors of the fallopian tube were the likely precursors of ovarian cancer and could directly give rise to metastatic lesions. These analyses suggest that there may be less than two years between the development of a STIC and the initiation of fallopian tube tumors, ovarian tumors or other metastases. Thus there may be a short window between the development of a STIC and the initiation of ovarian tumors or other metastases, highlighting the importance of the prevention, early detection and therapeutic intervention of this disease.

    RESPONSE TO EGFR BLOCKADE
    3.
    发明公开
    RESPONSE TO EGFR BLOCKADE 审中-公开

    公开(公告)号：US20240344136A1

    公开(公告)日：2024-10-17

    申请号：US18516168

    申请日：2023-11-21

    申请人： The Johns Hopkins University ,  University of Torino

    发明人： Victor E. Velculsecu ,  Eniko Papp ,  Vilmos Adleff ,  Andrea Bertotti ,  Livio Trusolino

    IPC分类号： C12Q1/6886 ,  A61K39/00 ,  A61K39/395 ,  A61P35/00 ,  C07K16/28 ,  C12Q1/68

    CPC分类号： C12Q1/6886 ,  A61K39/395 ,  A61P35/00 ,  C07K16/2863 ,  C12Q1/68 ,  A61K2039/505 ,  A61K2039/55 ,  C07K2317/24 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158

    摘要： Recent large-scale analyses have demonstrated that the genomic landscape of human cancer is complex and variable among individuals of the same tumor type. Such underlying genetic differences may in part be responsible for the varying therapeutic responses observed in cancer patients. To examine the effect of somatic genetic changes in colorectal cancer on sensitivity to a common targeted therapy, we performed complete exome sequence and copy number analyses of 129 tumors that were KRAS wild-type and analyzed their response to anti-EGFR antibody blockade in patient-derived tumorgraft models. In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy. Alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumors with increased sensitivity to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome in tumorgraft models through combinatorial therapies targeting actionable genes. These analyses provide a systematic approach to evaluate response to targeted therapies in human cancer, highlight additional mechanisms of responsiveness to anti-EGFR therapies, and provide additional avenues for intervention in the management of colorectal cancer.

    Genomic Alterations in the Tumor and Circulation of Pancreatic Cancer Patients
    5.
    发明申请
    Genomic Alterations in the Tumor and Circulation of Pancreatic Cancer Patients 审中-公开

    公开(公告)号：US20180155770A1

    公开(公告)日：2018-06-07

    申请号：US15552076

    申请日：2016-02-18

    申请人： The Johns Hopkins University

    发明人： Victor Velculescu ,  Mark Sausen ,  Vilmos Adleff ,  Jillian Phallen

    IPC分类号： C12Q1/6827 ,  C12Q1/6886 ,  C12Q1/6816

    CPC分类号： C12Q1/6827 ,  C12Q1/6816 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/156

    摘要： Pancreatic adenocarcinoma has the worst overall mortality of any solid tumor, with only 7% of patients surviving after 5 years. To evaluate the clinical implications of genomic alterations in this low cellularity tumor type, we deeply sequenced the genomes of 101 enriched pancreatic adenocarcinomas from patients who underwent potentially curative resections and used non-invasive approaches to examine tumor specific mutations in the circulation of these patients. These analyses revealed somatic mutations in chromatin regulating genes including MLL and ARID1A in 20% of patients that were associated with improved survival. Liquid biopsy analyses of cell free plasma DNA revealed that 43% of patients with localized disease had detectable circulating tumor DNA (ctDNA) in their blood at the time of diagnosis. Detection of ctDNA after resection predicted clinical relapse and poor outcome, and disease recurrence by ctDNA was detected 6.5 months earlier than with standard CT imaging.

    Response to EGFR blockade
    6.
    发明授权
    Response to EGFR blockade 有权

    公开(公告)号：US11845994B2

    公开(公告)日：2023-12-19

    申请号：US17225717

    申请日：2021-04-08

    申请人： The Johns Hopkins University ,  University of Torino

    发明人： Victor E. Velculescu ,  Eniko Papp ,  Vilmos Adleff ,  Andrea Bertotti ,  Livio Trusolino

    IPC分类号： C12Q1/6886 ,  A61K39/395 ,  C07K16/28 ,  C12Q1/68 ,  A61P35/00 ,  A61K39/00

    CPC分类号： C12Q1/6886 ,  A61K39/395 ,  A61P35/00 ,  C07K16/2863 ,  C12Q1/68 ,  A61K2039/505 ,  A61K2039/55 ,  C07K2317/24 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/158

    摘要： Recent large-scale analyses have demonstrated that the genomic landscape of human cancer is complex and variable among individuals of the same tumor type. Such underlying genetic differences may in part be responsible for the varying therapeutic responses observed in cancer patients. To examine the effect of somatic genetic changes in colorectal cancer on sensitivity to a common targeted therapy, we performed complete exome sequence and copy number analyses of 129 tumors that were KRAS wild-type and analyzed their response to anti-EGFR antibody blockade in patient-derived tumorgraft models. In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy. Alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumors with increased sensitivity to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome in tumorgraft models through combinatorial therapies targeting actionable genes. These analyses provide a systematic approach to evaluate response to targeted therapies in human cancer, highlight additional mechanisms of responsiveness to anti-EGFR therapies, and provide additional avenues for intervention in the management of colorectal cancer.

    GENOMIC ALTERATIONS IN THE TUMOR AND CIRCULATION OF PANCREATIC CANCER PATIENTS
    7.
    发明申请
    GENOMIC ALTERATIONS IN THE TUMOR AND CIRCULATION OF PANCREATIC CANCER PATIENTS 有权

    公开(公告)号：US20210108256A1

    公开(公告)日：2021-04-15

    申请号：US17080201

    申请日：2020-10-26

    申请人： The Johns Hopkins University

    发明人： Victor E. Velculescu ,  Mark Sausen ,  Vilmos Adleff ,  Jillian A. Phallen

    IPC分类号： C12Q1/6827 ,  C12Q1/6886 ,  C12Q1/6816

    摘要： Pancreatic adenocarcinoma has the worst overall mortality of any solid tumor, with only 7% of patients surviving after 5 years. To evaluate the clinical implications of genomic alterations in this low cellularity tumor type, we deeply sequenced the genomes of 101 enriched pancreatic adenocarcinomas from patients who underwent potentially curative resections and used non-invasive approaches to examine tumor specific mutations in the circulation of these patients. These analyses revealed somatic mutations in chromatin regulating genes including MLL and ARID1A in 20% of patients that were associated with improved survival. Liquid biopsy analyses of cell free plasma DNA revealed that 43% of patients with localized disease had detectable circulating tumor DNA (ctDNA) in their blood at the time of diagnosis. Detection of ctDNA after resection predicted clinical relapse and poor outcome, and disease recurrence by ctDNA was detected 6.5 months earlier than with standard CT imaging.

    RESPONSE TO EGFR BLOCKADE
    10.
    发明申请
    RESPONSE TO EGFR BLOCKADE 有权

    公开(公告)号：US20210301352A1

    公开(公告)日：2021-09-30

    申请号：US17225717

    申请日：2021-04-08

    申请人： The Johns Hopkins University ,  University of Torino

    发明人： Victor E. Velculescu ,  Eniko Papp ,  Vilmos Adleff ,  Andrea Bertotti ,  Livio Trusolino

    IPC分类号： C12Q1/6886 ,  A61K39/395 ,  C07K16/28 ,  C12Q1/68 ,  A61P35/00

    摘要： Recent large-scale analyses have demonstrated that the genomic landscape of human cancer is complex and variable among individuals of the same tumor type. Such underlying genetic differences may in part be responsible for the varying therapeutic responses observed in cancer patients. To examine the effect of somatic genetic changes in colorectal cancer on sensitivity to a common targeted therapy, we performed complete exome sequence and copy number analyses of 129 tumors that were KRAS wild-type and analyzed their response to anti-EGFR antibody blockade in patient-derived tumorgraft models. In addition to previously identified genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary resistance to this therapy. Alterations in the ectodomain of EGFR were identified in patients with acquired resistance to EGFR blockade. Amplifications and sequence changes in the tyrosine kinase receptor adaptor gene IRS2 were identified in tumors with increased sensitivity to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome in tumorgraft models through combinatorial therapies targeting actionable genes. These analyses provide a systematic approach to evaluate response to targeted therapies in human cancer, highlight additional mechanisms of responsiveness to anti-EGFR therapies, and provide additional avenues for intervention in the management of colorectal cancer.