| Term | Definition |
|---|
| The Origin of cancer | multi-step carcinogenesis, source of mutations, tumor initiation and progression |
| The "hallmarks" of cancer | Cells: proliferation, reduced cell death, cell survival, motility; Microenvironment: angiogenesis, invasion, metastatsis; Tumor heterogeneity and tumor stem cells |
| The basis of cancer treatment | Tumor burden, therapeutic modality |
| Cancer aging statistics | Cancer is a disease of aging: >70% cancer patients are 65+ years old; By 2030 25% of population will be over 65; Cancer is a "disease of aging" = takes time |
| Number of genetic hits required for cancer may vary depending on? | 1. Origin of tissue types: brain tumors (early onset) vs. prostate cancer (late onset) 2. Genetic make up of individual = presence of "genetic modifiers": family susceptible to cancer (early onset) vs. family resistant to cancer (late onset to no cancer) 3. life style choices: obesity linked to ovarian and other cancer. Smokers high risk for lung cancer. |
| Sources of mutations: | 1. Endogenous (internal) damage: Cellular metabolism: depurination, deamination, oxygen free radicals. DNA replication errors: point mutations, strand slippage, reduplication of genome. Chromosome segregation errors: aneuploidy |
| What is "mutator phenotype" | Mutates at a high rate due to the mutations in DNA repair pathway genes (>130 genes so far). Some results in genomic instability not being able to repair DNA breaks. |
| What are some Hereditary diseases that have a mutator phenotype resulting in cancer | Xeroderma Pigmentosum (XP) - Nucleotide excision repair --> Skin Cancer. Ataxia Telangiectasia (AT) - Double strand breaks --> Lymphomas. Bloom syndrom - Homologous recombination --> Leukemia, lymphoma, others. Li-Fraumeni syndrome - DNA repair check point --> wide spectrum of tumors. BRCA1/BRCA2 - Double strand breaks --> Breast cancer, ovarian cancer, others. Hereditary non-polyposis colorectal cancer - mismatch repair --> colorectal cancer. |
| Tumor initiators | Do not directly cause tumors but evidenced by the presence of mutations in tumors. Mostly mutagens, effects are rapid and irreversible. |
| Tumor promoters | Expands the population of initiated cells. Do not directly cause genomic mutations. Often alters gene expression and epigenetic events. Takes a period of time to take an effect. Early stage of the effects is largely reversible. |
| Importance of tumor microenvironment. Roles of "promoter" and more | Crosstalk from stroma: - Paracrine loop (growth stimuli) - Establishment of extracellular matrix (structural support) - induction of tumor (mCAF studies). Endothelial cells: Tumor Angiogenesis: delivery of oxygen and nutrients, essential for sustained growth, necrotic tumor core results without it. Immune cells: Cytokine production: Pro-growth, Pro-metastatic. |
| How does cancer kill patients? | * Tumor burden = the number of cancer cells * Invasion of surrounding tissue: obscured resection boundaries (brain tumors) * Obstruction of vital organ functions * Metastasis that leads to organ failure. |
| Cancer treatment modality | * Surgery: Most effective in lowering tumor burden * Chemotherapy: targeting rapidly growing tumor cells. Toxicity problem since these also target normally regenerating cells such as hair, skin, intestinal, blood cells. Also drug resistance problem. * Radiation therapy: Local ablation of rapidly growing tumor cells. * Hormonal therapy: Hormone specific antagonists. * Immuno therapy: Antibody against tumor-specific antigen. * Molecular target therapy: to be covered in the "oncogene" lecture. |
| The summary of lecture | * Cancer rises from a multi-step process that accumulates DNA mutations. * Cells that gain a proliferative advantage are clonally selected and expanded at each step in carcinogenesis. * Each tumor is composed of different types of cells: Through rapid expansion, each cell may take a distinct pathway resulting in tumor heterogeneity. * Chemotherapeutic drugs target proliferating cells thus, are also toxic to the normal cells that regenerate. Take home: prevention, early detection, and cancer therapeutics that target the hallmarks of cancer other than proliferation. |
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