Target: renal cancer

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FACULTY OF BIOCHEMISTRY, BIOPHYSICS AND BIOTECHNOLOGY

 

Renal cancer accounts for approximately 3% of all cases of malignant cancer in humans. Nearly 70-80% of cases are clear cell Renal Cell Carcinoma (ccRCC). A team of scientists from Kraków is working on a comprehensive analysis of this type of cancer, with the aim of looking for solutions that will contribute to the development of more effective therapy.

The symptoms of renal cancer usually occur as the disease progresses, so the main problem of patients with this type of cancer is delayed diagnosis, typically in the stage when the cancer has already metastasized to other organs. Clear cell renal cell carcinoma spreads particularly to the bones, lungs, brain and spinal cord.

Causes and treatment

In the case of primary renal cancer the treatment of choice is the surgical removal of the whole or part of the organ (radical or partial nephrectomy). Surgery is also applied if single metastatic areas are detected. As chemotherapy and radiation therapy that have been used so far do not bring satisfactory results, scientists are searching for new, more effective treatment methods. Much attention has been paid to the development of genetic tests, which will allow for the identification of individuals at risk of the development of clear cell renal cell carcinoma in screening tests and of biochemical analyses which will make it possible to determine the grade of malignancy of the tumour and its development stage along with the prognosis of the occurrence of metastases. It is supposed that one of the genes located on the short-arm of chromosome 3 is responsible for the development of clear cell renal cell carcinoma. Specific changes in the genetic material located in this chromosome are observed in approximately 50% of patients with clear cell renal cancer.

In comparison with other types of cancer, in the case of ccRCC the mechanism of recurrence has not been explained yet. Effective treatment of ccRCC consists of subjecting patients to so-called targeted therapy. It is based on detailed characteristics of the tumour in individual stages of development.


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Triple impact

The research on renal cancer consists of three modules, carried out in separate institutions: pathomorphological research at the Centre of Oncology in Kraków, genetic research at the Institute of Zoology of the Jagiellonian University and molecular analysis conducted at the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University. Biological material in the form of cancerous tissue along with histologically unchanged adjacent tissue of the organ is collected from patients of the Centre of Oncology by the team supervised by Professor Andrzej Stelmach, and then – upon the consent of the patient and the Ethics Committee – it is used for detailed analysis.

Microscopic analysis of the tumour includes an assessment of the stage of development carried out according to WHO classification and the evaluation of its mitotic activity, i.e. the capacity for cell division. On the other hand, confirmation of the presence of a characteristic arrangement of proteins is necessary in order to confirm the morphological diagnosis of the cancer. These analyses are conducted by a team of pathomorphologists supervised by Professor Janusz Ryś at the Centre of Oncology in Kraków.

Genetic tests include the search for genetic markers, which are characteristic DNA sequences or a specific arrangement of such sequences, existing in the genetic material collected from patients with identified clear cell renal cell carcinoma. These data are collected by the team supervised by Wojciech Branicki, PhD, specialist in the field of analyzing the differences in DNA sequences. The genetic analyses encompass 150 unrelated patients diagnosed with ccRCC and three hundred control samples collected from unrelated healthy persons. The objective of the studies will be to identify genetic markers that might be used in screening tests in the future, which will allow for earlier identification of people with a predisposition for this type of cancer.

The biological material collected from patients (cancerous tissue and healthy tissue adjacent to the tumour) is also subject to molecular analysis. This part of the research, co-ordinated by Professor Jolanta Jura, is carried out at the Department of General Biochemistry at the Faculty of Biochemistry, Biophysics and Biotechnology. Part of the molecular studies involves the analysis of the level of activity of selected genes coding proteins that are important in tumour development and the correlation of the activity of such genes with the development stage of cancer. Analyses carried out thus far prove that, in spite of the fact that based on histopathological tests clear cell renal cell carcinoma is classified as a homogeneous cancer, we are dealing with two forms of clear cell cancer which differ by the level of some matrices coding proteins that are significant for the transformations of this type of cancer.

On the hunt for a certain protein

"Within the scope of the molecular analyses, we are also planning to focus on the role of the MCPIP1 protein, whose level in cancer tissue is lower than in healthy tissue. This protein is a negative regulator of inflammatory processes, which are also important in the etiology, i.e. the analysis of causes for the occurrence of cancers. It is likely that the MCPIP1 protein may be used for the purposes of the preparation of anti-cancer treatment," Professor Jolanta Jura explains. But before this happens, complex research is necessary in order to explain its function in the regulation of the processes occurring in cancer cells. Previous analyses show that increasing the amount of the MCPIP1 protein in cancer cells significantly delays their multiplication, at the same time being toxic to such cells. Scientists are planning to analyze the mechanism that leads to the occurrence of such processes.

"We hope that our research will bring us closer to understanding the etiology of clear cell renal cell carcinoma and allow for the development of detailed molecular characteristics. This will also be an attempt to find another means that will constitute the basis for the future development of an effective treatment," Professor Jura concludes.


Research team:

Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Kraków: Professor Jolanta Jura; Janusz Ligęza, PhD; Barbara Lipert, MSc; Agnieszka Bojko, MSc; Anna Adamczyk, MSc

Institute of Zoology of the Jagiellonian University: Wojciech Branicki, PhD; Ewelina Pośpiech, PhD; Aniela Gołas, PhD Centre for Oncology, Kraków: Professor Andrzej Stelmach; Janusz Jaszczyński, PhD; Wacław Wilk, MD; Professor Janusz Ryś