• AXL inhibition improves BRAF-targeted treatment in melanoma 

      Nyakas, Marta Sølvi; Fleten, Karianne Giller; Haugen, Mads Haugland; Engedal, Nikolai; Sveen, Christina; Farstad, Inger Nina; Flørenes, Vivi Ann; Prasmickaite, Lina; Mælandsmo, Gunhild Mari; Vasiliauskaite, Kotryna (Journal article; Tidsskriftartikkel; Peer reviewed, 2022)
      More than half of metastatic melanoma patients receiving standard therapy fail to achieve a long-term survival due to primary and/or acquired resistance. Tumor cell ability to switch from epithelial to a more aggressive mesenchymal phenotype, attributed with AXL<sup>high</sup> molecular profle in melanoma, has been recently linked to such event, limiting treatment efcacy. In the current study, ...
    • Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4 

      Prasmickaite, Lina; Tenstad, Ellen; Pettersen, Solveig; Jabeen, Shakila; Egeland, Eivind Valen; Nord, Silje; Pandya, Abhilash D.; Haugen, Mads Haugland; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Engebråten, Olav; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-05-09)
      The tumor microenvironment (TME) may influence both cancer progression and therapeutic response. In breast cancer, particularly in the aggressive triple‐negative/basal‐like subgroup, patient outcome is strongly associated with the tumor's inflammatory profile. Tumor‐associated macrophages (TAMs) are among the most abundant immune cells in the TME, shown to be linked to poor prognosis and therapeutic ...
    • Biodistribution of Poly(alkyl cyanoacrylate) Nanoparticles in Mice and Effect on Tumor Infiltration of Macrophages into a Patient-Derived Breast Cancer Xenograft 

      Pandya, Abhilash D.; Iversen, Tore Geir; Moestue, Siver Andreas; Grinde, Maria Tunset; Mørch, Ýrr Asbjørg; Snipstad, Sofie; Åslund, Andreas; Øy, Geir Frode; Kildal, Wanja; Engebråten, Olav; Sandvig, Kirsten; Skotland, Tore; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-28)
      We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl cyanoacrylate), in mice. These NPs are structurally similar, have similar PEGylation, and have previously been shown to give large variations in ...
    • Breast cancer patient-derived explant cultures recapitulate in vivo drug responses 

      Pettersen, Solveig; Øy, Geir Frode; Egeland, Eivind Valen; Juell, Siri; Engebråten, Olav; Mælandsmo, Gunhild Mari; Prasmickaite, Lina (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-02-22)
      Assessment of drug sensitivity in tumor tissue ex vivo may significantly contribute to functional diagnostics to guide personalized treatment of cancer. Tumor organoid- and explant-cultures have become attractive tools towards this goal, although culturing conditions for breast cancer (BC) tissue have been among the most challenging to develop. Validation of possibilities to detect concordant responses ...
    • Cabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograft 

      Fusser, Markus; Øverbye, Anders; Pandya, Abhilash D.; Mørch, Ýrr Asbjørg; Borgos, Sven Even F.; Kildal, Wanja; Snipstad, Sofie; Sulheim, Einar; Fleten, Karianne Giller; Askautrud, Hanne Arenberg; Engebraaten, Olav; Flatmark, Kjersti; Iversen, Tore Geir; Sandvig, Kirsten; Skotland, Tore; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-04)
      The effect of poly(2-ethyl-butyl cyanoacrylate) nanoparticles containing the cytotoxic drug cabazitaxel was studied in three breast cancer cell lines and one basal-like patient-derived xenograft model grown in the mammary fat pad of immunodeficient mice. Nanoparticle-encapsulated cabazitaxel had a much better efficacy than similar concentrations of free drug in the basal-like patient-derived xenograft ...
    • A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression 

      Ghannoum, Salim; Fantini, Damiano; Zahoor, Muhammad; Reiterer, Veronika; Phuyal, Santosh; Leoncio Netto, Waldir; Sørensen, Øystein; Iyer, Arvind; Sengupta, Debarka; Prasmickaite, Lina; Mælandsmo, Gunhild Mari; Kohn Luque, Alvaro; Farhan, Hesso (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-04-17)
      Our understanding of how speed and persistence of cell migration affects the growth rate and size of tumors remains incomplete. To address this, we developed a mathematical model wherein cells migrate in two-dimensional space, divide, die or intravasate into the vasculature. Exploring a wide range of speed and persistence combinations, we find that tumor growth positively correlates with increasing ...
    • Correlation of expression of Major Vault Protein with androgen receptor and immune checkpoint protein B7-H3, and with poor prognosis in prostate cancer 

      Nunes-Xavier, Caroline Elisabeth; Emaldi, Maite; Guldvik, Ingrid Jenny; Ramberg, Håkon; Tasken, Kristin Austlid; Mælandsmo, Gunhild Mari; Fodstad, Øystein; Llarena, Roberto; Pulido, Rafael; Lopez, José I. (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-11-24)
      Prostate cancer diagnosis and early stratification is an important aspect to avoid undertreatment of high-risk prostate cancer patients. Major Vault Protein (MVP) has been proposed as a prognostic biomarker in prostate cancer. PTEN and the immune checkpoint protein B7-H3 interact with MVP and are important in prostate cancer progression and therapy response. We evaluated the expression of MVP by ...
    • Cost-effectiveness of molecularly matched off-label therapies for end-stage cancer–the MetAction precision medicine study 

      Ree, Anne Hansen; Mælandsmo, Gunhild Mari; Flatmark, Kjersti; Russnes, Hege Elisabeth Giercksky; Casteneda, Monica Gomez; Aas, Eline (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-09)
      Background: Precision cancer medicine (PCM), frequently used for the expensive and often modestly efficacious off-label treatment with medications matched to the tumour genome of end-stage cancer, challenges healthcare resources. We compared the health effects, costs and cost-effectiveness of our MetAction PCM study with corresponding data from comparator populations given best supportive care ...
    • Design, synthesis and biological evaluation of 6‐substituted quinolines derived from cabozantinib as c‐Met inhibitors 

      Lien, Vegard Torp; Pettersen, Solveig; Haugen, Mads Haugland; Olberg, Dag Erlend; Mælandsmo, Gunhild Mari; Klaveness, Jo (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-15)
      Based on the cabozantinib scaffold, novel c‐Met inhibitors were rationalized from the limited knowledge of structure‐activity relationships for the quinoline 6‐position. Emphasis was given to modifications capable of engaging in additional polar interactions with the c‐Met active site. In addition, <i>ortho</i>‐fluorinations of the terminal benzene ring were explored. Fifteen new molecules were ...
    • Detection of phenotype-specific therapeutic vulnerabilities in breast cells using a CRISPR loss-of-function screen 

      Barkovskaya, Anna; Goodwin, Craig; Seip, Kotryna; Hilmarsdòttir, Bylgja; Pettersen, Solveig; Stalnecker, Clint; Engebraaten, Olav; Briem, Eirikur; Der, Channing J; Moestue, Siver Andreas; Guðjónsson, Þórarinn; Mælandsmo, Gunhild Mari; Prasmickaite, Lina (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-24)
      Cellular phenotype plasticity between the epithelial and mesenchymal states has been linked to metastasis and heterogeneous responses to cancer therapy, and remains a challenge for the treatment of triple-negative breast cancer (TNBC). Here, we used isogenic human breast epithelial cell lines, D492 and D492M, representing the epithelial and mesenchymal phenotypes, respectively. We employed a CRISPR-Cas9 ...
    • Drug-Loaded Photosensitizer-Chitosan Nanoparticles for Combinatorial Chemo- and Photodynamic-Therapy of Cancer 

      Pandya, Abhilash D.; Øverbye, Anders; Sahariah, Priyanka; Gaware, Vivek S.; Høgset, Håkon; Masson, Már; Høgset, Anders; Mælandsmo, Gunhild Mari; Skotland, Tore; Sandvig, Kirsten; Iversen, Tore Geir (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-02-24)
      In this study we have developed biodegradable polymeric nanoparticles (NPs) containing the cytostatic drugs mertansine (MRT) or cabazitaxel (CBZ). The NPs are based on chitosan (CS) conjugate polymers synthesized with different amounts of the photosensitizer tetraphenylchlorin (TPC). These TPC–CS NPs have high loading capacity and strong drug retention due to π–π stacking interactions between the ...
    • The expression of the long NEAT1_2 isoform is associated with human epidermal growth factor receptor 2-positive breast cancers 

      Knutsen, Erik; Lellahi, Seyed Mohammad; Aure, Miriam Ragle; Nord, Silje; Fismen, Silje; Larsen, Kenneth Bowitz; Tellez Gabriel, Marta; Hedberg, Annica; Bjørklund, Sunniva; Bofin, Anna M.; Mælandsmo, Gunhild Mari; Sørlie, Therese; Mortensen, Elin Synnøve; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-01-28)
      The long non-coding RNA <i>NEAT1</i> locus is transcribed into two overlapping isoforms, <i>NEAT1_1</i> and <i>NEAT1_2</i>, of which the latter is essential for the assembly of nuclear paraspeckles. <i>NEAT1</i> is abnormally expressed in a wide variety of human cancers. Emerging evidence suggests that the two isoforms have distinct functions in gene expression regulation, and recently it was shown ...
    • The expression pattern of pyruvate dehydrogenase kinases predicts prognosis and correlates with immune exhaustion in clear cell renal cell carcinoma 

      Nunes-Xavier, Caroline Elisabeth; Emaldi, Maite; Mingo, Janire; Øyjord, Tove Ragnhild; Mælandsmo, Gunhild Mari; Fodstad, Øystein; Errarte, Peio; Larrinaga, Gorka; Llarena, Roberto; López, José I.; Pulido, Rafael (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-05-05)
      Renal cancer cells constitute a paradigm of tumor cells with a glycolytic reprogramming which drives metabolic alterations favouring cell survival and transformation. We studied the expression and activity of pyruvate dehydrogenase kinases (PDK1-4), key enzymes of the energy metabolism, in renal cancer cells. We analysed the expression, subcellular distribution and clinicopathological correlations ...
    • Fibroblast growth factor 2 conjugated with monomethyl auristatin E inhibits tumor growth in a mouse model 

      Krzyscik, Mateusz Adam; Zakrzewska, Malgorzata; Sørensen, Vigdis; Øy, Geir Frode; Bruheim, Skjalg; Haugsten, Ellen Margrethe; Mælandsmo, Gunhild Mari; Wiedlocha, Antoni; Otlewski, Jacek (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-20)
      Worldwide, cancer is the second leading cause of death. Regardless of the continuous progress in medicine, we still do not have a fully effective anti-cancer therapy. Therefore, the search for new targeted anti-cancer drugs is still an unmet need. Here, we present novel protein–drug conjugates that inhibit tumor growth in a mouse model of human breast cancer. We developed conjugates based on fibroblast ...
    • Glutamine to proline conversion is associated with response to glutaminase inhibition in breast cancer 

      Grinde, Maria Tunset; Hilmarsdòttir, Bylgja; Tunset, Hanna Maja; Henriksen, Ida Marie; Kim, Jana; Haugen, Mads Haugland; Rye, Morten Beck; Mælandsmo, Gunhild Mari; Moestue, Siver Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-05-14)
      <p><i>Introduction - </i>Glutaminase inhibitors target cancer cells by blocking the conversion of glutamine to glutamate, thereby potentially interfering with anaplerosis and synthesis of amino acids and glutathione. The drug CB-839 has shown promising effects in preclinical experiments and is currently undergoing clinical trials in several human malignancies, including triple-negative breast cancer ...
    • High-throughput screen in vitro identifies dasatinib as a candidate for combinatorial treatment with HER2-targeting drugs in breast cancer 

      Normann, Lisa Svartdal; Haugen, Mads; Hongisto, Vesa; Aure, Miriam Ragle; Leivonen, Suvi-Katri; Kristensen, Vessela N.; Tahiri, Andliena; Engebråten, Olav; Sahlberg, Guro Kristine Kleivi; Mælandsmo, Gunhild Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-01-27)
      Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype of this disease. Targeted treatment has improved outcome, but there is still a need for new therapeutic strategies as some patients respond poorly to treatment. Our aim was to identify compounds that substantially affect viability in HER2+ breast cancer cells in response to combinatorial treatment. We ...
    • Identification of a core EMT signature that separates basal-like breast cancers into partial- and post-EMT subtypes 

      Knutsen, Erik; Sajib, Saikat Das; Fiskaa, Tonje; Lorens, James Bradley; Gudjonsson, Thorarinn; Mælandsmo, Gunhild Mari; Johansen, Steinar Daae; Seternes, Ole Morten; Perander, Maria (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-04)
      Epithelial-mesenchymal transition (EMT) is a cellular plasticity program critical for embryonic development and tissue regeneration, and aberrant EMT is associated with disease including cancer. The high degree of plasticity in the mammary epithelium is reflected in extensive heterogeneity among breast cancers. Here, we have analyzed RNA-sequencing data from three different mammary epithelial cell ...
    • Liver X receptors induce antiproliferative effects in basal-like breast cancer 

      Haugen, Mads; von der Lippe Gythfeldt, Hedda; Egeland, Eivind Valen; Svartdal Normann, Lisa; Pandya, Abhilash D.; Vedin, Lise-Lotte; Juell, Siri; Tenstad, Ellen; Øy, Geir Frode; Kristian, Alexandr; Marangoni, Elisabetta; Sørlie, Therese; Steffensen, Knut Rune; Mælandsmo, Gunhild Mari; Engebråten, Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-21)
      Liver X receptors (LXRs) are nuclear transcription factors important in the regulation of cholesterol transport, and glucose and fatty acid metabolism. The antiproliferative role of LXRs has been studied in a variety of malignancies and may represent a therapeutic opportunity in cancers lacking targeted therapies, such as triple-negative breast cancer. In this study, we investigated the impact of ...
    • miR-101-5p Acts as a Tumor Suppressor in HER2-Positive Breast Cancer Cells and Improves Targeted Therapy 

      Normann, Lisa Svartdal; Haugen, Mads Haugland; Aure, Miriam Ragle; Kristensen, Vessela N.; Mælandsmo, Gunhild Mari; Sahlberg, Kristine Kleivi (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-03-01)
      Purpose: Human epidermal growth factor receptor 2 positive (HER2+) breast cancers responding poorly to targeted therapy need improved treatment options. miR-101-5p has shown tumor-suppressive properties in multiple cancer forms, and we assessed the effect and mechanism of action of this miRNA in HER2+ breast cancer.<p> <p>Methods: Expression levels of miR-101-5p in two clinical datasets, TCGA and ...
    • Molecularly matched therapy in the context of sensitivity, resistance, and safety; patient outcomes in end-stage cancer - the MetAction study 

      Ree, Anne Hansen; Nygaard, Vigdis; Pedersen, Kjetil Boye; Heinrich, Daniel; Dueland, Svein; Bergheim, Inger Riise; Johansen, Christin; Beiske, Klaus; Negård, Anne; Lund-Iversen, Marius; Nygaard, Vegard; Hovig, Eivind; Nakken, Sigve; Nasser, Salah; Julsrud, Lars; Reisse, Claudius; Ruud, Espen Asak; Kristensen, Vessela N.; Flørenes, Vivi Ann; Geitvik, Gry; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise; Russnes, Hege Elisabeth Giercksky; Mælandsmo, Gunhild Mari; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-25)
      <i>Background</i>: In precision cancer medicine, the challenge is to prioritize DNA driver events, account for resistance markers, and procure sufficient information for treatment that maintains patient safety. The MetAction project, exploring how tumor molecular vulnerabilities predict therapy response, first established the required workflow for DNA sequencing and data interpretation (2014–2015). ...