Ateneo - UPO

1. The epidemiological significance of cancer; the influence of environment and lifestyle; 2. The main histopathological characteristics of tumors and their classification; 3. Molecular alterations responsible for the malignant behavior of tumor cells (loss of proliferative control, resistance to apoptosis, invasiveness, altered metabolism of glucose, amino acids, and fatty acids, disruption of proteomic homeostasis); the role of autophagy and cell death in cancer; 4. The role of genetics and epigenetics in cancer development and progression; genetic defects predisposing to cancer; genomic alterations (chromosomal translocations) and gene mutations (oncogenes, tumor suppressor genes) associated with cancer; 5. The origin and phenotypic characteristics of cancer stem cells; genetic and metabolic reprogramming leading to cancer; 6. Mechanisms of metastasis formation; the role of proteolytic enzymes; 7. Interactions between tumor cells and the tumor stroma, with particular regard to the role of cancer-associated fibroblasts and immune cells; 8. Molecular and pathophysiological mechanisms responsible for cachexia syndrome; 9. Current diagnostic techniques (imaging, biomarkers) and available therapeutic treatments (chemotherapy, biomolecular therapy); 10. Novel therapeutic approaches (epigenetics); new paradigms of carcinogenesis (microbiome).

The Molecular Biology of Cancer S-Pelengaris and M. Khan (Wiley-Blackwell edition)

The course will provide students with fundaments of general oncology and knowledge about cellular and molecular mechanisms involved in carcinogenesis, as well as about experimental approaches in the field of oncological research. Recognize the histopathological characteristics of the main human neoplasms; Understand which molecular and cellular alterations determine the neoplastic phenotype; Reason about the natural causes of carcinogenesis and the factors that can determine tumor recurrence, keeping in mind the role of defense systems at the molecular, cellular and organismal level; Describe the distinctive characteristics (morphological, metabolic, behavioral) of neoplastic stem cells. Know the mechanisms responsible for tumor infiltration and metastasis; Be able to illustrate how the stromal microenvironment that surrounds the tumor changes and how this can favor neoplastic growth. Recognize the clinical signs and be able to describe the molecular and physiopathological mechanisms of neoplastic cachexia. EXPECTED KNOWLEDGE AND SKILLS At the end of the course the student must be able to tackle the reading and analysis of scientific articles on the cellular and molecular biology of neoplasms (during the course each student must present a scientific article related to a topic covered). Learning outcomes: Knowledge of the cellular and molecular mechanisms underlying the carcinogenesis process. Dynamics of neoplastic populations. Natural history of neoplasms. Risk factors for the development of neoplasms.

The students must possess the basic knowledge in cell and molecular biology and in biochemistry.

Interactive lesson continuously involving students with questions to stimulate curiosity and verify the understanding of concepts. Process illustration with practical examples. Discussion of relevant scientific articles.

Students are welcome to spend a period in the laboratory of Molecular Pathology to participate in the design, execution and discussion of experiments. CFU will be assigned based on the duration of the stage. Students will be involved in Journal Club meetings in which scientific papers relevant for their preparation will be discussed.

The student can choose between two exam formats (“Basic” or “Advanced”), according to the level of preparation they believe they have reached. All written and oral questions are chosen from a list of questions made available on the teacher's website, in order to allow the student to take a self-assessment test. The "Basic" format consists of a written test which is not followed by the oral exam. The assignment consists of 5 “true or false statements” and the student will have to answer 4 questions justifying the answer with a supporting explanation in about 10 lines. You have 1 hour at your disposal. The correct and exhaustive answer is worth 6 points (maximum achievable score 24/30). The topics of the "Basic" program include nomenclature, epidemiology, cytological and histological characteristics, characteristics of the malignant phenotype, chemical and radiation carcinogenesis, glucose metabolism. The "Advanced" format includes a written assignment with 3 questions (30 minutes) followed by an oral exam (3 questions) and the discussion of a scientific article (as desired, from a list prepared by the teacher). The "Advanced" exam program integrates the "basic" with an in-depth study of the alterations of the molecular signaling pathways; cell cycle control; telomerase; cancer stem cell; the role of genomic, genetic, and epigenetic mutations; alterations in the (glucose, amino acid and lipid) metabolism of the cancer cell; the molecular and metabolic bases of neoplastic cachexia; new diagnostic and therapeutic approaches. The maximum score is 30 + Laude / 30. NOTE: 1. the final score is agreed between the two teachers of modules A and B, taking into account the overall assessments; 2. if only one of the two modules (A or B) is not passed, the student must repeat the exam for both modules (A and B) in a new session.NOTE: To access the exam the student must have filled up the course evaluation form.

1.Introduction to Cancer. Definition, Epidemiology. Features overview of benign and malignant tumors. Solid tumors: parenchyma and stroma. Examples of tumors.
2. Natural history of cancer: multistage carcinogenesis, genetic and epigenetic modifications; clonal expansion; mutations, risk factors.
3. Nomenclature, Histopathology. Classification, Staging, Grading.
4. Genetic and chromosome instability. DNA repair.
5. Familial and Genetic syndromes predisposing to cancer.
6. Oncogenes (classification). Main Oncogenes: c-MYC, RAS, BCL-2, BRAF, and others. Oncogene addiction. Signaling pathways
7. Tumour Suppressors. Main Tumour Suppressor genes: TP53, PTEN, BECLIN1, BRCA1, TSC, and others. Signaling pathways
8. Epigenetics and Cancer. DNMT, HDAC, microRNAs.
9. Control of cell proliferation, cell cycle; Telomerase
10. Control of cell homeostasis; control of macromolecular turnover; Autophagy; Control of Cell death (Apoptosis, Necrosis, Autophagic cell death).
11. Tumor Dormancy, cancer cell dormancy, cell senescence, Cancer Stem Cells.
12. Cancer cell metabolism: Glucose (Warburg effect), Amino Acids, Lipids.
13. Influence of oncogenes and oncosuppressors on cancer cell metabolism.
14. Tumour stroma. Cancer associated fibroblasts. Cancer inflammation. Immune response.
15. Cell adhesion. Invasion and Metastasis. Angiogenesis.
16. Cancer aetiology; Gene – environment interaction; Lifestyle and Cancer (smoke, diet, alcohol).
17. Genotoxic and NON-genotoxic carcinogenesis (examples). Chemical Carcinogenesis. Indirect and Direct chemical carcinogens. DMS activation/excretion of chemical carcinogens. Nitrous Bases adducts.
18. Multistage carcinogenesis (initiation, promotion, progression. Cancer progression and Concept of clonal evolution
19. Infections and cancer; parasite infestation and cancer. Virus and carcinogenesis. Physical causes of cancer. Mineral fibers (Asbestos and mesothelioma pathogenesis). Radiation and cancer: direct and indirect effects. Ionizing radiation. UV radiation.
20. Chemotherapy and Mechanisms of chemoresistance.
21. Cachexia and Anorexia in cancer patients. Cori’s cycle; adipose tissue metabolism.

Knowing the causes and mechanisms of carcinogenesis and tumor progression. Knowing how to interpret, discuss and present the experimental laboratory results or found in literature, specifically aimed at describing and understanding the neoplastic transformation and behavior of tumor cells.