• Concomitant inactivation of the p53- and pRB- functional pathways predicts resistance to DNA damaging drugs in breast cancer in vivo 

      Knappskog, Stian; Berge, Elisabet Ognedal; Chrisanthar, Ranjan; Geisler, Stephanie; Staalesen, Vidar; Leirvaag, Beryl; Yndestad, Synnøve; de Faveri, Elise Norheim; Karlsen, Bård Ove; Wedge, David C.; Akslen, Lars A.; Lilleng, Peer Kåre; Løkkevik, Erik; Lundgren, Steinar; Østenstad, Bjørn; Risberg, Terje; Mjaaland, Ingvil; Aas, Turid; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-05-08)
      Chemoresistance is the main obstacle to cancer cure. Contrasting studies focusing on single gene mutations, we hypothesize chemoresistance to be due to inactivation of key pathways affecting cellular mechanisms such as apoptosis, senescence, or DNA repair. In support of this hypothesis, we have previously shown inactivation of either TP53 or its key activators CHK2 and ATM to predict resistance ...
    • Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer 

      Yndestad, Synnøve; Engebrethsen, Christina; Herencia-Ropero, A.; Nikolaienko, Oleksii; Vintermyr, Olav Karsten; Lillestøl, Reidun Kristine; Minsaas, Laura; Leirvaag, Beryl; Iversen, Gjertrud Titlestad; Gilje, Bjørnar; Blix, Egil Støre; Espelid, Helge; Lundgren, Steinar; Geisler, Jürgen; Aase, Hildegunn Siv; Aas, Turid; Gudlaugsson, Einar; Llop-Guevara, Alba; Serra, Violeta; Janssen, Emiel; Lønning, Per Eystein; Knappskog, Stian; Eikesdal, Hans Petter (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-01)
      Purpose - Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD in non-TNBC to assess the potential for PARPi in a wider group of patients with breast cancer.<p> <p>Methods - HRD status was established using targeted gene panel sequencing (360 genes) and ...
    • Olaparib monotherapy as primary treatment in unselected triple negative breast cancer 

      Eikesdal, Hans Petter; Yndestad, Synnøve; Elzawahry, Asmaa; Llop-Guevara, Alba; Gilje, Bjørnar; Blix, Egil Støre; Espelid, Helge; Lundgren, Steinar; Geisler, Jürgen; Vagstad, Geirfinn; Venizelos, Andreas; Minsaas, Laura; Leirvaag, Beryl; Gudlaugsson, Einar; Vintermyr, Olav Karsten; Aase, Hildegunn Siv; Aas, Turid; Balmaña, Judith; Serra, Violeta; Janssen, Emiel; Knappskog, Stian; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-11-23)
      <p><i>Background - </i>The antitumor efficacy of PARP inhibitors (PARPi) for breast cancer patients harboring germline BRCA1/2 (gBRCA1/2) mutations is well established. While PARPi monotherapy was ineffective in patients with metastatic triple negative breast cancer (TNBC) wild type for BRCA1/2, we hypothesized that PARPi may be effective in primary TNBCs without previous chemotherapy exposure. < ...
    • Predictive and Prognostic Impact of TP53 Mutations and MDM2 Promoter Genotype in Primary Breast Cancer Patients Treated with Epirubicin or Paclitaxel 

      Chrisanthar, Ranjan; Knappskog, Stian; Løkkevik, Erik; Anker, Gun Birgitta; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Skjønsberg, Gudbrand; Aas, Turid; Schlichting, Ellen; Fjøsne, Hans Erikssønn; Nysted, Arne; Lillehaug, Johan R.; Lønning, Per Eystein (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP) T309G increases MDM2 activity and may reduce wildtype p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer ...