Keynote Conference - Interevent

Symp#18 Perspectives in cancer therapies
Chair Jörg Kobarg
Prospecting and testing new molecular target proteins for cancer therapy: integrating systems and structural
biology”
Jörg Kobarg, PhD
LNBio-Laboratório Nacional de Biociências, CNPEM-Centro Nacional de Pesquisa em Energia e Materiais
Rua Giuseppe Máximo Scolfaro 10.000 Campinas-SP, Brasil, CEP 13083-970 F: 0055-19-3512-1125
Starting from identified cancer related proteins or candidate proteins we explore and integrate several techniques and
approaches ranging from structural biology, micro array, proteomics, protein interactome to cellular and molecular
functional characterization, in order to obtain information on the mechanisms underlying the dysfunction of these
proteins in cancer and to envision new modes of interference aiming at the target specific therapeutic intervention in
cancer. Distinct aspects of this approach are exemplified by three different proteins or groups of proteins currently
under investigation: 1. FEZ1 as a kinesin associated transport adaptor protein that when over-expressed can lead to
the formation of so called “flower-like nuclei“, a hall mark of certain aggressive sub-types of leukemia. 2. Il-7 Receptor
Cys insertion mutations that lead to aberrant receptor homo-dimerization and constitutive activation , growth and
survival of lymphocytes and to tumor formation in the mice model. 3. The 11 human members of the family of NIMA
(Never in mitosis gene A)-related serine/threonine kinases (Neks) have cell cycle-related functions, were recently
described as related to pathologies, particularly cancer, and present promissing chemotherapeutic targets. In order to
understand better the cellular functions of human Nek kinases we performed yeast two-hybrid assays using Nek1, 6, 7
and 9 as baits to identify their protein interaction partners. Similar studies are currently ongoing for Nek 3, 4, 5, 10 and
11. We will present a general overview of our results and their implications for these protein kinases functions in the
context of tumorigenesis.
Modern optical techniques for diagnostic and treatment of cancer and microorganisms
Vanderlei S. Bagnato
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, Brazil
Solving health problems with photonics techniques is attractive due to its more selective and fast response, minimally
or non-invasive procedure, and potential low cost instrumentation. These characteristics are especially relevant for
emergent economy countries, where health care is still deficient for large amount of population. Brazil shows a diverse
situation along its large territory: it is possible to find the best medicine with the highest technology available and well
educated personnel, but also a poor health care or even the lack of one. Diagnostics and treatment techniques that are
effective, low cost, and that requires simple instrumentation may be good solutions for improving health care. This
presentation will start with the main principles involved in photonics for live science and present the status of
development for applications in cancer diagnostic and treatmne as well as microbial control.
Deciphering Neuregulin-HER signaling in breast cancer
Atanasio Pandiella
Centro de Investigación del Cancer. CSIC-Universidad de Salamanca, Spain.
The ErbB/HER receptors and their ligands play important roles in animal physiology, and their deregulation has been
linked to diseases such as cancer. Activation of the HER receptors may occur by different mechanisms, including ligand
binding, receptor overexpression, or molecular alterations. In breast cancer, one of the HER family recptors, termed
HER2, is overexpressed in tumors of 20% of patients, and this has led to the development of therapies against HER2
which are now routinely used in the breast cancer clinic. While assessment of the levels of HER receptors in breast
cancer has been extensively analyzed, the role of their ligands has been less well studied. We have explored the
expression of Neuregulins (NRGs), a subgroup of HER ligands, in breast cancer samples. We observed frequent
expression of these ligands, and such expression was linked to metastatic dissemination and poor clinical outcome,
indicating that targeting this ligand system may be therapeutically beneficial. For this reason, we have started a
program to identify how the NRG-HER signaling system controls the proliferation of breast cancer cells. Genomic as
well as proteomic strategies have allowed us to identify novel signaling intermediates of the NRG-HER system. Using
biochemical, genetic, cell biological techniques, as well as xenografted mice, we have elucidated the participation of
these novel signaling intermediates in NRG-stimulated proliferative responses in breast cancer cells. Pharmacological
action on some of these intermediates allowed us to evaluate the potential therapeutic value of their targeting in
breast cancer.
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