Rolf Lewensohn's Group

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Development of novel treatments for lung cancer. Our aim is to develop new oncological treatments in the form of novel drug candidates and precision radiotherapy, with a personalized cancer medicine approach.

From all types of cancer, lung cancer is the leading cause of cancer-related mortality. Each year approximately 1.4 million people die worldwide because of lung cancer. Possibilities to increase survival of lung cancer patients are rapidly emerging. Early stages of lung cancer in the form of a localized intra-thoracic tumor or a tumor with a limited number of metastases may now be attacked with curative intent. However, lung cancer is often detected only at a late stage. Moreover, after an initial response to treatment, therapy-resistant clones inevitably start growing resulting in rapid disease progression. New knowledge of lung cancer-specific mutations, identification of biomarkers to predict therapy response, and understanding of the molecular mechanisms of action of novel drugs opens up for personalization of treatment.

A number of novel drug candidates, among which some are reacting with tumor DNA and/or directed to interfering with DNA repair, are being developed in our laboratory through a full preclinical test system preceding clinical trials. This includes analysis of biochemical mechanisms of action of these drugs and identification of corresponding putative biomarkers to create precision in selecting patients with sensitive tumors for a specific treatment. The research comprises of work on primary tumor material, biobanking thereof, genomics and proteomics analyses, and also in vivo experiments to determine proof-of-principal and pharmacological parameters. We have brought one compound Mel-flufen, which is a conjugate of a peptide and a DNA-alkylator, to phase II clinical trial.

In parallel, we run clinical trials on lung cancer in our clinical trial unit at Karolinska university hospital, in collaboration with pharmaceutical partners. A clinical trial program on precision-based hypofractionated radiotherapy (SBRT) is ongoing and rapidly being further developed. SBRT seems promising in treatment of inoperable tumors, to improve lung cancer survival. In several clinical trials, drug and radiotherapy are also combined as a novel strategy to cure cases with both early localized and early metastasized disease.

Furthermore, the group has a leading role in EurocanPlatform, an EU-funded project to bring together 28 European cancer institutions and organizations, with the aim to improve outcomes for cancer patients and reduce mortality. Within the Karolinska Institutet and Karolinska university hospital, Prof. Lewensohn is the primary initiator of the development of a personalized cancer medicine program. The ultimate goal of this program is to quickly and efficiently translate the latest scientific advances into a concrete improvement of the care for cancer patients.

The descriptions of the ongoing research projects provide more detailed information:

Projects

Dissertations

The following PhD-students completed their thesis under supervision of Rolf Lewensohn and/or Kristina Viktorsson as the main and/or co-supervisor:

Marita Lagergren Lindberg
Acute myeloid leukemia - Apoptotic signalling and gene expression associated with treatment response.
2013-11-15
Abstract and thesis

Hogir Salim
Identification of novel tumor biomarkers for sensitivity to radio- and chemotherapy of lung cancer based on genomic analyses.
2013-10-24
Abstract and thesis

Nadeem S Akbar
microRNAs: significance for sensitivity/resistance of lung cancer cells to treatment
2013-01-24
Abstract and thesis

Dali Zong
Molecular characterization of phenothiazines in experimental cancer therapy - New tricks of an old drug revealed
2012-04-25
Abstract and thesis

Kah Wai Lin
Proteomics of invasiveness of human breast epithelial cells
2012-02-24
Abstract and thesis

Betzabe Chavez Sanches
Customization of tamoxifen therapy: not only a dream
2011-09-06
Abstract and thesis

Sara Ståhl
Signalomics: unsupervised and global strategies to explore mechanisms of radioresistance in lung cancer cells
2011-06-01
Abstract and thesis

Olena Zakharchenko
Proteome profiling of human breast cancer
2011-04-11
Abstract and thesis

Catharina Beskow
Outcome of preoperative radiotherapy in the treatment of cervical cancer with focus on protein expression and dosimetry
2011-01-12
Abstract and thesis

Luigi De Petris
Discovery and validation of protein biomarkers for lung cancer
2010-09-08
Abstract and thesis

Maria Pernemalm
Cancer proteomics: method development for mass spectrometry based analysis of clinical materials
2009-11-06
Abstract anc thesis

Sara Jonmarker Jaraj
Tissue biomarkers in prostate cancer
2009-10-16
Abstract and thesis

Pia Baumann
Stereotactic body radiotherapy in non-small cell lung cancer
2009-04-03
Abstract and thesis

Lukas Orre
Proteomic analysis of DNA damage induced stress signaling with focus on p53: S100A6 regulation, function and potential as biomarker in lung cancer and as a novel therapeutic target
2008-05-23
Abstract and thesis

Irina Radulescu
Induction and repair of DNA double-strand breaks in human cells exposed to different radiation qualities
2008-02-22
Abstract and thesis

Mia Carapancea
Strategies to increase effectiveness of growth factor receptors-targeted therapy in glioblastoma (licentiate thesis)
2007-12-05
Abstract and thesis

Annica Jernberg
Ultrasound, ions and combined modalities for increased local tumour cell death in radiation therapy
2007-05-03
Abstract and thesis

Daria Cosaceanu
The use of IGF-IR inhibitors in cancer therapy: a potential approach for sensitizing tumor cells to ionizing radiation
2006-09-15
Abstract and thesis

Jeffrey R. Yachnin
Chemical, pharmacokinetic and biological aspects of platinum-based drugs
2005-05-06
Abstract and thesis

Roger Tell
Description and prediction of clinical radiosensitivity
2004-03-19
Abstract

Anya Polischouk
Molecular factors relevant to the radiosensitivity of human tumours
2003-06-06
Abstract

Jessica Ekedahl
Apoptotic signaling in lung carcinoma cells: With focus on mechanisms of radioresistance
2003-05-23
Abstract

Åsa Holgersson
DNA-dependent protein kinase in normal and malignant cells, with special reference to anti-tumour agent sensivity
2003-01-24
Abstract

Signe Friesland
Factors of importance for radiosensitivity of tonsillar carcinoma
2002-06-14
Abstract

Florin Sirzén
Molecular aspects of cellular radiosensitivity in small cell lung carcinoma
1998-12-04
Abstract

Björn Cedervall
Analysis of X-ray induced DNA double-strand breaks using pulsed field gel electrophoresis
1995-06-15

Jan-Olof Fernberg
On melphalan treatment in multiple myeloma: a clinical and experimental study
Sept 1992

Funding

Group members

Rolf Lewensohn, MD, PhD, Professor, Principal Investigator
Kristina Viktorsson, PhD, Senior Researcher, Principal Investigator
Petra Hååg, PhD, Assistant Professor
Lena Kanter, MD, PhD, Pathologist
Luigi De Petris, MD, PhD, Oncologist, Post doc 
Ana Zovko, PhD, Post doc
Metka Novak, PhD, Post doc
Katarzyna Zielinska-Chomej, MSc, PhD student
Ghazal Efazat, MSc, PhD student
Carl-Henrik Shah, MD, PhD student
Karin Lindberg, MD, PhD student
Salomon Tendler, MD, PhD student
Therese Juntti, Biomedical Research Assistant
Liselotte Hälleberg, Research Coordinator 
Christina von Gertten, PhD, EU Project Manager, Research Coordinator
Pieter de Koning, PhD, Grant Advisor, Project Coordinator
Michele Masucci, MSc, Project Coordinator
David Keros, MSc, Health Informatician 

Selected publications

miRNA-214 is related to invasiveness of human non-small cell lung cancer and directly regulates alpha protein kinase 2 expression.
Salim H, Arvanitis A, de Petris L, Kanter L, Hååg P, Zovko A, et al
Genes Chromosomes Cancer 2013 Oct;52(10):895-911

APS8, a polymeric alkylpyridinium salt blocks α7 nAChR and induces apoptosis in non-small cell lung carcinoma.
Zovko A, Viktorsson K, Lewensohn R, Kološa K, Filipič M, Xing H, et al
Mar Drugs 2013 Jul;11(7):2574-94

In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells.
Chauhan D, Ray A, Viktorsson K, Spira J, Paba-Prada C, Munshi N, et al
Clin. Cancer Res. 2013 Jun;19(11):3019-31

Resistance to DNA-damaging treatment in non-small cell lung cancer tumor-initiating cells involves reduced DNA-PK/ATM activation and diminished cell cycle arrest.
Lundholm L, Hååg P, Zong D, Juntti T, Mörk B, Lewensohn R, et al
Cell Death Dis 2013 ;4():e478

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy.
Peulen H, Karlsson K, Lindberg K, Tullgren O, Baumann P, Lax I, et al
Radiother Oncol 2011 Nov;101(2):260-6

Essential role for DNA-PK-mediated phosphorylation of NR4A nuclear orphan receptors in DNA double-strand break repair.
Malewicz M, Kadkhodaei B, Kee N, Volakakis N, Hellman U, Viktorsson K, et al
Genes Dev. 2011 Oct;25(19):2031-40

Phosphoproteomic profiling of NSCLC cells reveals that ephrin B3 regulates pro-survival signaling through Akt1-mediated phosphorylation of the EphA2 receptor.
Ståhl S, Branca R, Efazat G, Ruzzene M, Zhivotovsky B, Lewensohn R, et al
J. Proteome Res. 2011 May;10(5):2566-78

Chemosensitization by phenothiazines in human lung cancer cells: impaired resolution of γH2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation.
Zong D, Hååg P, Yakymovych I, Lewensohn R, Viktorsson K
Cell Death Dis 2011 ;2():e181

Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.
Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi G, Lax I, et al
J. Clin. Oncol. 2009 Jul;27(20):3290-6

Proteomics and pathway analysis identifies JNK signaling as critical for high linear energy transfer radiation-induced apoptosis in non-small lung cancer cells.
Ståhl S, Fung E, Adams C, Lengqvist J, Mörk B, Stenerlöw B, et al
Mol. Cell Proteomics 2009 May;8(5):1117-29

Full list of publications from Rolf Lewensohn

Lung cancer