Learning Outcomes:
1. to undestand processes that lead to tumor formation on molecular and cellular level
2. to undestant tje connection between malingnant transformation and genetic changes
3. to understand properties of tumor cells
4. to know current therapeutical strategies
5. to recommend targeted terapies based on change in cell signaling
6. to perform mutagenesis testing
7. to perform cytotoxycity testing
Course Content:
1. Basic definition of histopathologic and molecular tumor classification - histologic tumor type, tumor grade, TNM classification and molecular-based classification. Types of treatment - chemotherapy, radiation therapy, biological therapy (targeted, immunotherapy, differentiation therapy)
2. Types of carcinogenesis - chemical carcinogenesis caused by chemicals, infectious caused by bacteria and viruses, caused by aging and endogenous metabolic processes and carcinogenesis caused by exposure to UV radiation and ionizing radiation
3. Causes of genetic instability - changes in the genome (mutations, amplifications, rearrangements). Epigenetic regulation of gene expression, telomerase activity and epigenetic therapies.
4. Oncogenes and tumor suppressor genes - the definition and role in carcinogenesis. EGFR signaling pathway, changes in the signaling pathway in tumors and therapies that target this pathway. Knudson two hit hypothesis, hereditary syndromes and sporadic cases of tumors associated with inactivation of tumor suppressors.
5. Cell cycle regulation - phases of the cell cycle, the cyclin-CDK complexes and their regulation, the passage of cells through the mitotic checkpoint. The role of the Rb protein and Aurora kinases.
6. Evasion of apoptosis - a type of cell death, regulation of cell death, changes in tumors and targeted therapies. The role of the p53 protein and its regulation.
7. Stem cell differentiation and cancer stem cells - the characteristics of stem cells, self-renewal signaling pathways, the role of cancer stem cells in tumor regenerate, metastasis and resistance to chemotherapy and radiotherapy. Block in differentiation as a cause of leukemia
8. Invasiveness, metastasis and angiogenesis - the invasion, Intravasation, transport, extravasation and metastatic colonization as the steps of metastasis, the characteristics of each step, epithelial-mesenchymal transition. Ways to create blood network in tumors, angiogenesis, vasculogenesis, vascular mimicry, intususeption, the bloodstream grab. Anti-angiogenic therapy, and reasons of resistance.
9. Changing the metabolism of cancer cells - Warburg effect, glucose metabolism, positron emission tomography based on increased intake of glucose, metabolic therapy
10. Maintenance of chronic inflammation and avoiding host immune responses - dual role of the immune system in carcinogenesis. Inflammation as a cause of cancer via NFkappaB. Three phases of immune editing: elimination, equilibrium and escape. Immunotherapy - Therapeutic vaccines based on dendritic cells and peptides, monoclonal antibodies and inhibition of immunosuppression.
11. Synthesis of the course through analysis of breast, lung and skin cancers - Breast cancer and hormonal carcinogenesis, histological and molecular types of breast cancer, therapy depending on the receptor status. Lung cancer and chemical carcinogenesis, cigarette smoking as a cause of lung cancer, histologic types and signaling pathways in lung cancer.
12. Food and cancer - food as a cause of cancer and chemoprevention, nutrigenomics.
Lab work:
1. Ames test for screening of mutagens. Students use adryamicin, MNNG and substance of their choice.
2. MTT viability testin of tumor cell line after treatment with chemotherapeutic drug
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