1 / 9

Molecular Biomarkers in Radiotherapy of Cervical Cancer

Molecular Biomarkers in Radiotherapy of Cervical Cancer. A collaboration project between Department of Gynecologic Oncology and Department of Radiation Biology. Project group The Radiation Therapy Team at Dept. of Gynecologic Oncology /Gunnar B. Kristensen, Dr. Med

tkeasler
Download Presentation

Molecular Biomarkers in Radiotherapy of Cervical Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Molecular Biomarkers in Radiotherapy of Cervical Cancer A collaboration project between Department of Gynecologic Oncology and Department of Radiation Biology Project group The Radiation Therapy Team at Dept. of Gynecologic Oncology /Gunnar B. Kristensen, Dr. Med The Clinical Radiation Biology Group at Dept. of Radiation Biology /Heidi Lyng, Dr. Philos

  2. Lymph nodes External radiation, field_1 front Radiation field Radiotherapy of cervical carcinomas Need for improved treatment – more individualized therapy based on biological information External irradiation: Tumour region (50 Gy) and the rest of pelvis (45 Gy) Endocavitary brachytherapy: Cervix (21 Gy) Narrow therapeutic window  high frequency of side effects to pelvic organs

  3. Microarrays MR imaging MR-spectroscopy Aims Molecular methods based on microarrays will be combined with MR and eventually PET techniques to find biomarkers that can be utilized for biologically optimized therapy • Identify predictive biomarkers for the therapeutic outcome, including patient survival, locoregional tumor control and normal tissue side effects. • Identify key radiation regulated pathways in tumors and possible targets for molecular intervention. • Explore how the molecular findings can be combined with functional (MR and PET) and molecular imaging in treatment planning and response monitoring.

  4. CT dose plan Radiation therapy, curative intent T2-MRI DCE-MRI Tumor biopsies Clinical data base Pathology MR/CT findings Radiation field Follow-up Research projects MedInsight Study protocol on cervical cancer, stage 2b-4a DCE-MRI Blood sample Tumor biopsies >300 patients included Image storage Blood and tissue storage

  5. Tumor biopsies Molecular screening Signaling Studies in cell lines Functional imaging DCE-MRI Research projects Normal tissue side effects CT dose plan, blood samples

  6. Analysis of tumor biopsies Genuttrykk (mRNA) ”New” genes Marker for clinical outcome? Terapeutic target? Collaboration with statisticians Frigessi, Glad, Holden: UiO, NR Van de Wiel, Vrije Universiteit, Amsterdam Frigessi et al, Nucleic Acids Res, 2005 Scheel et al, Bioinformatics, 2005 Ferkingstad et al., Genome Biology, 2008 Nygaard et al., BMC Genomics, 2008 Molecular screening - gene profile associated with clinical outcome - basis for further molecular studies Classification of patients with different outcome based on gene profile Gene profile 1 Gene profile 2 P = 0.02 PhD student Malin Lando

  7. 1 3 5 7 9 11 13 15 17 19 21 X 2 4 6 8 10 12 14 16 18 20 22 C 22% 44% 34% -1pcen-31 +1q -6q24-25 -12q -17p -19p -1pcen-31 +1q -6q24-25 -12q -17p -19p -1pcen-31 +1q -6q24-25 -12q -17p -19p Subpopulations of tumor cells with different genetic characteristics -13qcen-34 -13qcen-34 -1p31-ter -2q21-ter -4p +6p -8p Evolution Lyng et al., Genome Biology 2008 Molecular screening: intratumor heterogeneity in gene copy number Genome wide screening of copy number in cervix tumor B A C024/01 DNA index: 1.00 Tumor cell fraction: 55% 2&3 2 1&2 Frequency (%) aCGH ratio (log2) 2&3 1 3 1&2 1&2 aCGH ratio (log2) Chromosomal location 1pter-Xqter Pronounced heterogeneity in copy number within cervix tumors → resistent subpopulations may emerge at later stages of the disease

  8. Score N Events 0-6 87 37 9 72 15 MSN Screening  signaling Analysis of tumor biopsies Characterization of signaling pathways of importance for outcome → mechanisms of activation PhD student Cathinka Halle Collaboration with Division of Pathology Ruth Holm Low MSN expression → poor outcome High MSN expression Low MSN expression Progression free survival P = 0.004 Time (months) Lyng et al., BMC Genomics, 2006

  9. Tumor biopsy from cervix cancer Metabolic profile 200 B ● 150 Lac 100 ● FA – CH = CH – CH2 – CH2 Glycerol backbone TSP Predicted apoptotic cell density (cells/mm2) Cre GPC FA – (CH2)n FA – CH2 –CH2 –CO- FA –CH2 –CH3 ● PC 50 ● FA – CH3 Ac ● Tau ● Cho ● Cre ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● r = 0.95 p < 0.001 ● Gly ● ● ● 0 ● ● ● Metabolites involved in treatment induced apoptosis ● ● ● Lac ● ● ● -Glc -50 Measured apoptotic cell density (cells/mm2) -20 0 20 40 60 80 100 120 140 160 180 200 Lyng et al., BMC Cancer 2007 4.4 4.0 3.6 3.2 2.8 2.4 2.0 1.6 1.2 0.8 0.4 0.0 (ppm) Metabolic screening by use of MR-spectroscopy - relationship to molecular data, imaging (MR) and clinical data Collaboration with the MR center in Trondheim Ingrid Gribbestad

More Related