Characteristics of normal and transformed cells. Molecular bases of cellular transformation. Oncogenes, antioncogenes, DNA repair, metabolic and death/survival genes: their roles in mechanisms that control or promote transformation. Stem cells and cancer. Alterations in signals that control cell growth and proliferation. Viral and cellular oncogenes: homologies and differences. Mertabolic factors and “Warburg” effect. Role of mitochondria and oxidative stress. The pathways activated by hypoxic and Wnt signaling.
“Sporadic” and “hereditary” tumors. Autosomal-dominant syndromes: the retinoblastoma model and the RB1 gene; the familial adenomatous polyposis model, the APC gene and the WNT pathway model; Lynch syndrome (HNPCC) and mismatch repair genes; hereditary breast cancer and the BRCA1/BRCA2 and TP53 genes; Von-Hippel lindau syndrome and the VHL gene model; hereditary pheochromocytoma/paraganglioma syndromes and nuclear genes encoding OXPHOS chain components. Xeroderma pigmentosum and nuclear excision repair genes as a model of predisposition to cutaneous tumors by ultraviolet radiation.
Benign and malignant tumors. Complete histogenetic classification of benign and malignant human tumors in relation to site of origin and staging. Molecular mechanisms implicated in invasion and metastasis: general concepts. Primary and metastatic tumors. Metastatic spread in relation to tumor type and anatomic site. Concept of stadiation (TNM). Elements of cancer epidemiology.
Chemical and environmental carcinogenesis. Concepts of tumor initiation and promotion. Principal direct and indirect chemical carcinogens, their modes of action and risk factors. Carcinogenesis by ultraviolet and ionizing radiation. Assays for the evaluaion of transforming activity. Tobacco and cancer.
Viral carcinogenesis. Mechanisms of transformation by DNA and RNA tumor viruses. “Acute” and “chronic” transforming retroviruses: their historic role in the identification of cancer-related cellular genes. Oncogenic viruses associated to human tumors: papilloma viruses, herpesviruses, hepatitis virus, HTLV1, HIV1.
