Plexins and semaphorins in cancer diagnostics and therapy
Semaphorins and their receptors plexins/neuropilins are expressed aberrantly in several (e.g. brain, breast and lung) cancers, and are therefore suitable targets for diagnosis as well as therapy. We have identified that the expression of plexin B3 is altered in gliomas. Understanding of such expression patterns yields the basis for planned applied research on novel diagnostic and therapeutic tools.
The objective of the project is the development of RT-PCR and immunohistochemistry-based diagnostic methods for profiling of all semaphorins, plexins and neuropilins.
In addition, a research on recombinant extracellular domains (SEMA) of above mentioned molecules as decoys to repress tumor development will be performed.
Molecular diagnostics for personalised therapy
The project is focused on the development of molecular diagnostics in personalized therapy. Pharmacogenetics is a rapidly developing field that has important implications in individualized treatment for patients.
During the project two approaches for colorectal cancer and lung cancer testing will be developed and implemented into clinical practice. Study of molecular profiling on 200 solid tumor samples will be performed. High-Resolution Melting analysis will be used for tumor molecular profiling.
Results of study will give important information for development of strategies for treatment optimization based on the compatibility between the molecular profile of the disease and the drug to be administered. Approaches for colorectal and lung cancer testing will provide actionable results in a concise, patient-specific, correlated report with clinically relevant information to assist treatment decisions. Also the study benefits the molecular diagnostic strategy for diagnosing hereditary non-polyposis colorectal cancer.
Project will give economy of public funds for cancer therapy in medicine due to implementation of better and more economic personalized therapy schemes.
Blood tests for breast cancer
The aim of the project is to identify biomarkers and develop diagnostic tests for early detection, diagnosis and treatment monitoring for breast cancer from blood sera. Existing breast cancer diagnostic methods are based on imaging and biopsy that implies that cancer has to have imagable size to be detected. Relaltively late detection of cancer reduces the efficiency of the treatment since in many cases the process of metastasis starts early. Moreover, current diagnostic methods are in majority of cases not useful for treatment monitoring.
The blood-based diagnostic test that monitors patient’s immune system response to cancer will enable to detect cancer early, characterize each individual cancer at the molecular level and aid to the selection of appropriate treatment options.
During the years of 2009-2013, it is planned to identify a set of biomarkers and validate the clinical use of these biomarker sets for:
prognosis of neoadjuvant treatment of breast cancer.
Identification of biomarkers for early detection of colorectal cancer
DIAMUT Development of early cancer diagnostics based on molecular profiling of solid tumors
The current medical focus has been centered on early cancer detection that enables curative treatment to be administered before cancer progresses to late stage. Screening for cancer is still a complex issue and evidently a need exists for better biomarkers to improve the detection of cancer in early stage. Project DIAMUT is focused on development of biomarkers systems for screening colorectal cancer.
Colorectal cancer develops through a complex interplay of genetic and epigenetic abnormalities that transform normal epithelium into dysplastic epithelium, which may ultimately progress into invasive and metastatic disease. These molecular aberrations induce the immune response against immunogenic epitopes of tumor-associated antigenes (TAAs) and cause the production of autoantibodies. Autoantibodies against autologus TAAs have been detected in the asymptomatic stage of cancer and can thus serve as biomarkers for early cancer diagnosis. Autoantibodies are found in serum, they can be screened easily using a noninvasive approach.
The aim of the project is to develop two biomarker systems for detecting colorectal cancer in early stage. Autoantibodies and T-cell receptors, which are correlated to genetic and epigenetic changes in tumor cells, will be identified and validated.
Modulation of miRNA levels in cancer cells
Modulation of miRNA levels in cancer cells During the last years the importance of small non-coding RNAs has been proven also in the case of cancer development. The normal levels of different microRNAs (miRNAs) are altered in cancer patients. Small RNAs, like miRNAs, are part of the RNA silencing mechanism. There are suppressor proteins that block RNA silencing pathways and change the pattern of small RNAs. Thus, using suppressors to target cancer-specific miRNAs has potential.
Suppressors of RNA silencing are known to modulate the levels of miRNAs in plants. Our results show that some viral RNAi suppressors as well as endogenous RNAi suppressors interfere with RNA silencing also in mammalian cells.
The objective of this project is to identify candidate drugs for cancer therapy that modulate oncogenic and/or tumor-suppressor miRNA levels. For this, a large number of suppressors are being tested in cell culture as well as in mouse model. In addition, cellular interactors of these suppressors will be identified. Based on the obtained results, a candidate drug (silencing suppressor or its fragment) as well as a candidate drug target (an interactor or its domain) will be provided.