Rolf Lewensohn's Group
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:
- Drug discovery and development of compounds from marine sponges
- Analysis of Ephrin/Eph receptor signaling networks in lung cancer
- Significance of microRNAs in lung cancer
- Characterization of lung cancer stem cells
- Chemo- and radiotherapy sensitizing strategies in lung cancer
- Phenothiazines as regulators of DNA repair in leukemia
- EurocanPlatform: a European platform for translational cancer research
The following PhD-students completed their thesis under supervision of Rolf Lewensohn and/or Kristina Viktorsson as the main and/or co-supervisor:
Katarzyna Zielinska-Chomej, 2015-10-16
Analysis and characterization of chemo- and radiation therapy sensitizing strategies in tumours with focus on effects of phenothiazines on DNA damage response signalling
Karin Lindberg, 2015-05-29
Stereotactic body radiation therapy of primary lung cancer and metastases
Marita Lagergren Lindberg, 2013-11-15
Acute myeloid leukemia - Apoptotic signalling and gene expression associated with treatment response
Nadeem S Akbar, 2013-01-24
microRNAs: significance for sensitivity/resistance of lung cancer cells to treatment
Kah Wai Lin, 2012-02-24
Proteomics of invasiveness of human breast epithelial cells
Betzabe Chavez Sanches, 2011-09-06
Customization of tamoxifen therapy: not only a dream
Olena Zakharchenko, 2011-04-11
Proteome profiling of human breast cancer
Luigi De Petris, 2010-09-08
Discovery and validation of protein biomarkers for lung cancer
Maria Pernemalm, 2009-11-06
Cancer proteomics: method development for mass spectrometry based analysis of clinical materials
Sara Jonmarker Jaraj, 2009-10-16
Tissue biomarkers in prostate cancer
Pia Baumann, 2009-04-03
Stereotactic body radiotherapy in non-small cell lung cancer
Lukas Orre, 2008-05-23
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
Irina Radulescu, 2008-02-22
Induction and repair of DNA double-strand breaks in human cells exposed to different radiation qualities
Annica Jernberg, 2007-05-03
Ultrasound, ions and combined modalities for increased local tumour cell death in radiation therapy
Jeffrey R. Yachnin, 2005-05-06
Chemical, pharmacokinetic and biological aspects of platinum-based drugs
Roger Tell, 2004-03-19
Description and prediction of clinical radiosensitivity
Anya Polischouk, 2003-06-06
Molecular factors relevant to the radiosensitivity of human tumours
Jessica Ekedahl, 2003-05-23
Apoptotic signaling in lung carcinoma cells: With focus on mechanisms of radioresistance
Signe Friesland, 2002-06-14
Factors of importance for radiosensitivity of tonsillar carcinoma
Florin Sirzén, 1998-12-04
Molecular aspects of cellular radiosensitivity in small cell lung carcinoma
Björn Cedervall, 1995-06-15
Analysis of X-ray induced DNA double-strand breaks using pulsed field gel electrophoresis
Jan-Olof Fernberg, 1992-09
On melphalan treatment in multiple myeloma: a clinical and experimental study
- Swedish Cancer Society
- Cancer Society in Stockholm
- King Gustaf V’s Jubilee Foundation
- Knut and Alice Wallenberg Foundation
- Stockholm County Council
- Stiftelsen för hematologisk forskning
- Karolinska Institutet
- European Union - Framework Program 7 (FP7)
- Swedish Radiation Safety Authority
Rolf Lewensohn, MD, PhD, Professor, Principal Investigator
Kristina Viktorsson, PhD, Senior Researcher, Principal Investigator
Petra Hååg, PhD, Assistant Professor
Per Hydbring, PhD, Assistant Professor
Lena Kanter, MD, PhD, Pathologist
Luigi De Petris, MD, PhD, Oncologist, Post doc
Metka Novak, PhD, Post doc
Katarzyna Zielinska-Chomej, MSc, PhD, Post doc
Adam Sierakowiak, PhD, Post doc
Carl-Henrik Shah, MD, PhD student
Simon Ekman, MD, Associated Professor, oncologist
Karin Lindberg, MD, PhD
Salomon Tendler, MD, PhD student
Georgios Tsakonas, MD, PhD student
Liselotte Hälleberg, Research Coordinator
Christina von Gertten, PhD, EU Project Manager, Research Coordinator
Long-term results of a prospective phase II trial of medically inoperable stage I NSCLC treated with SBRT - the Nordic experience.
Lindberg K, Nyman J, Riesenfeld Källskog V, Hoyer M, Lund JÅ, Lax I, et al
Acta Oncol 2015 ;54(8):1096-104
Marine sponge Cribrochalina vasculum compounds activate intrinsic apoptotic signaling and inhibit growth factor signaling cascades in non-small cell lung carcinoma.
Zovko A, Viktorsson K, Hååg P, Kovalerchick D, Färnegårdh K, Alimonti A, et al
Mol. Cancer Ther. 2014 Dec;13(12):2941-54
Harnessing the lysosome-dependent antitumor activity of phenothiazines in human small cell lung cancer.
Zong D, Zielinska-Chomej K, Juntti T, Mörk B, Lewensohn R, Hååg P, et al
Cell Death Dis 2014 Mar;5():e1111
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
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
Inhibition of Ephrin B3-mediated survival signaling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412.
Ståhl S, Kaminskyy VO, Efazat G, Hyrslova Vaculova A, Rodriguez-Nieto S, Moshfegh A, et al
Cell Death Dis 2013 Jan;4():e454
miRNA-214 modulates radiotherapy response of non-small cell lung cancer cells through regulation of p38MAPK, apoptosis and senescence.
Salim H, Akbar NS, Zong D, Vaculova AH, Lewensohn R, Moshfegh A, et al
Br. J. Cancer 2012 Oct;107(8):1361-73
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
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 Jul;2():e181
Phosphoproteomic profiling of NSCLC cells reveals that ephrin B3 regulates pro-survival signaling through Akt1-mediated phosphorylation of the EphA2 receptor.
Ståhl S, Branca RM, Efazat G, Ruzzene M, Zhivotovsky B, Lewensohn R, et al
J. Proteome Res. 2011 May;10(5):2566-78