Publications 2019

Hanes R, Munthe E, Grad I, Han J, Karlsen I, McCormack E, Meza-Zepeda LA, Stratford EW, Myklebost O (2019) Preclinical evaluation of the pan-FGFR inhibitor LY2874455 in FRS2-amplified liposarcoma. Special Issue “Fibroblast Growth Factor Receptor (FGFR) Signaling Pathway in Tumor: Cells 2019, 8(2), 189; PDF (Open Access) DOI:10.3390/cells8020189  

Myklebost O (Ed) Genomsekvensering for bedre persontilpasning av kreftbehandling. (100 p report from the Cancer Genomics Consortium in Norwegian) Jan 2019 pdf 

Publications 2018

Birkeland E, Zhang S, Poduval D, Geisler J, Nakken S, Vodak D, Meza-Zepeda LA, Hovig E, Myklebost O,Knappskog S, Lønning PE (2018) Patterns of genomic evolution in advanced melanoma. Nature Comm DOI: 10.1038/s41467-018-05063-1  

Gouravan S, Meza-Zepeda LA, Myklebost O, Stratford EW, Munthe E (2018) Preclinical evaluation of vemurafenib as therapy for BRAFV600E mutated sarcomas Int J Mol Sci DOI:10.3390/ijms19040969 

Kresse SK, Namløs HM, Lorenz S, Berner JM, Ola Myklebost O, Bjerkehagen B, Meza-Zepeda LA(2018) Evaluation of commercial DNA and RNA extraction methods for high-throughput sequencing of FFPE samples. PLoS One https://doi.org/10.1371/journal.pone.0197456 

Nakken S, Fournous G, Vodak D, Aasheim B, Myklebost O, Hovig E (2017) Personal Cancer Genome Reporter: Variant Interpretation Report For Precision Oncology. Bioinformatics 1–3 doi:10.1093/bioinformatics/btx817 

Namløs H, Boye K, Mishkin SJ, Barøy T, Lorenz S, Bjerkehagen B, Stratford EW, Munthe E, Kudlow BA, Myklebost O, Meza-Zepeda LA(2018) Non-invasive detection of ctDNA reveals intratumour heterogeneity and is significantly associated with aggressive GIST Mol Cancer Ther  10.1158/1535-7163.MCT-18-0174

Serguienko A, Wang MY, Myklebost O(2018) Real-time vital mineralization detection and quantification during in vitro osteoblast differentiation. Biological Procedures Online (2018) 20:14 DOI: 10.1186/s12575-018-0079-4 

Strauss SJ, Anninga J, Baglio B, Baumhoer D, Behjati S, Bielack S, Boye K, Broto JM, Cleton‑Jansen AM, Degasperi A, Evans A, Fagioli F, Fiocco M, Gaspar N, Heymann D, Hindi N, Lancia C, Myklebost O, Nathrath M, Redini F, Scotlandi K, Tirtei E, Vanden Eynden M, Whelan J (2018) Report from the 4th European Bone Sarcoma Networking meeting: focus on osteosarcoma Clin Sarcoma Res 8:17 DOI:10.1186/s13569-018-0103-0 

Vodák D, Lorenz S, Nakken S, Aasheim LB, Holte H, Bai B, Myklebost O, Meza-Zepeda LA, Hovig E (2018) Sample-Index Misassignment Impacts Tumour Exome Sequencing Sci. Rep. DOI:10.1038/s41598-018-23563-4 

 

Repurposing drugs for sarcoma patients

Like so many orphan, or neglected, cancers, therapies for sarcomas have, with a few exceptions, not improved much the last decades. Surgery, radiation and chemotherapy are the main treatment arms, but chemotherapy appears to have reached a limit due to high toxicities, and has not significantly improved this century. A notable exception is the treatment of GIST with drugs targeting the c-kit pathway, which is a prime example of successful repurposing of a drug. Imatinib was developed to target the fusion protein bcr-abl which causes leukemia, but turned out to also be very effective against the mutated kit receptor in GIST (gastrointestinal stromal tumours). We are trying to identify other such drugs, developed and perhaps approved for another cancer type, but having activity against sarcomas.

Candidate sarcoma drugs are identified by two main projects: Determining cancer mechanisms that are mutated in sarcomas, or drug screening of drug libraries on sarcoma cells in culture. In the first project we identify mutated mechanisms that have been exploited in therapies in other cancers. However, although we may find the same mutations that predict response in another cancer, this may not be the case in sarcomas. We therefore have to find one or more cell lines with this type of mutation, and test their sensitivity to the drug. If it works it is promising, but we still do not know if it will work in a patient, as there are so many differences between a cell culture and a body. Some of these issues may be accounted for by investigating the activity in a human sarcoma grown in mice, but still this is just a first stepping-stone for clinical trials, there are many differences between such an artificial experimental system and real tumours in patients.

To determine the efficacy in patients, a clinical trial has to be organised and funded.

NoSarC, – A national, prospective sarcoma study

NoSarC, – the NOrwegian SArcoma Consortium, is a collaboration between sarcoma scientists and clinics in all Norwegian health regions to collect and analyse samples form (almost) all sarcoma patients over 3 years. Depending on funding, we are determining all mutations in the tumours by “next generation sequencing” samples from tumours and blood in all cases where tumour is available.