Theocharis Panaretakis' Group
Exosome-based Biomarkers and Novel Cancer Therapies. Effective cancer therapy relies on two main parameters, early detection and effective eradication of the malignancy by inducing cancer cell death.
Tumor-derived Exosomes as the source of Diagnostic and Prognostic markers
One of our main research objectives is to identify novel, sensitive, cancer prognostic and diagnostic markers by investigating circulating, Tumor cell-derived EXosomes (TEX). Exosomes are the newest family of bioactive vesicles that function as a vehicle for cell-free intercellular communication. Exosomes are actively secreted by virtually all cell types, through exocytosis under normal as well as pathological conditions. In cancer patients secretion of TEX into biological fluids has been reported in various malignancies such lymphomas, leukemias, breast cancer and prostate cancer.
Novel Cancer Therapies
Induction of cancer cell death is one of the most prominent mechanisms activated by anti-cancer drugs. There are a number of ways by which clinically used anti-cancer drugs can induce cell death such as apoptosis, autophagy, necrosis and mitotic catastrophy.
The role of apoptosis, autophagy and necrosis, as well as their interplay, in response to anti-cancer therapy is the other main research objective of this group. Furthermore, being in close collaboration with medical doctors and pharmaceutical companies puts us in a unique position to identify and investigate novel cancer therapeutics that can be effective against various types of cancer.
In close collaboration with the Royal Institute of Technology and the Swedish Medical Nanoscience Center, novel nanoparticle-based drug carriers are being designed and investigated for their properties to create more efficient cancer therapeutics.
- Young Investigator Award 2010 from the Swedish Cancer Society
- The Swedish Cancer Society
- The Swedish Childhood Cancer Society
- The Swedish Cancer Foundation
- Royal Academy of Sciences
- Åke Wiberg funds
- Karolinska Institutet funds
- Svenska Läkaresällskapet
- Guido Kroemer, Institut Gustave Roussy, France
- Adi Kimchi, Weisman Institute, Israel
- Laurence Zitvogel, Institut Gustave Roussy, France
- Dan Grandér, Karolinska Institutet, Sweden
- Boris Zhivotovsky, Karolinska Institutet, Sweden
- Sten Nilsson, Karolinska Institutet, Sweden
- Anders Ullén, Karolinska Institutet, Sweden
- Magnus Björkholm, Karolinska Institutet, Sweden
- Anders Hult, Royal Institute of Technology, Sweden
- Michael Malkoch, Royal Institute of Technology, Sweden
- Lars Holmgren, Karolinska Institutet, Sweden
Activation of Bak, Bax, and BH3-only proteins in the apoptotic response to doxorubicin.
J. Biol. Chem. 2002 Nov;277(46):44317-26
Doxorubicin requires the sequential activation of caspase-2, protein kinase Cdelta, and c-Jun NH2-terminal kinase to induce apoptosis.
Mol. Biol. Cell 2005 Aug;16(8):3821-31
Calreticulin exposure dictates the immunogenicity of cancer cell death.
Nat. Med. 2007 Jan;13(1):54-61
The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death.
Cell Death Differ. 2008 Sep;15(9):1499-509
Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death.
EMBO J. 2009 Mar;28(5):578-90
Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy.
Cell Death Differ. 2009 Jul;16(7):1018-29
Autophagy as the main means of cytotoxicity by glucocorticoids in hematological malignancies.
Autophagy 2009 Nov;5(8):1198-200
Sorafenib has potent antitumor activity against multiple myeloma in vitro, ex vivo, and in vivo in the 5T33MM mouse model.
Cancer Res. 2012 Oct;72(20):5348-62