Molecular Biology of Cancer Exam 1 Flashcards
List the 10 defining characteristics of Cancer.
- Growth Signal Autonomy
- Growth Inhibitory Signals
- Avoiding Immune System Destruction
- Unlimited Replicative Potential
- Tumor-promoting Inflammation
- Invasion and Metastasis
- Angiogenesis
- Genomic Instability and Mutation
- Evasion of Cell Death
- Reprograming of Energy Metabolism
Describe Growth Signal Autonomy
●Normal cells need external signals from growth factors to divide
●Cancer cells are not dependent on normal growth factor signaling
●Acquired mutations (mutant oncogenes) short-circuit growth factor pathways leading to unregulated growth
Describe Evasion of Growth Inhibitory Signals
●Normal cells respond to inhibitory signals to maintain homeostasis (most cells of the body are not actively dividing)
●Cancer cells do not respond to growth inhibitory signals
●Acquired mutations (mutant tumor suppressor genes) or gene silencing interfere with the inhibitory pathways.
Describe Avoiding Immune System Destruction
●There is evidence to support the theory of immune surveillance-that the immune system can recognized and eliminate cancer cells.
●Successful cancer cell may be those that do not stimulate an immune response or can interfere with the immune response so as to avoid immune destruction.
Describe Unlimited Replicative Potential
●Normal cells have an autonomous counting device to define a finite number of cell doublings after which they become senescent. This cellular counting device is the shortening of chromosomal ends, telomeres, that occurs during every round of DNA replication
●Cancer cells maintain the length of their telomeres
●Altered regulation of telomere maintenance results in unlimited replication potential
Describe Tumor-promoting Inflammation
●Virtually all tumors contain inflammatory immune cells
●Inflammation is an immune response that can facilitate acquiring the core hallmarks of cancer. For example, inflammatory cells can provide growth factors and enzymes that promote angiogenesis and invasion
●In addition, inflammatory cells can release oxygen species that are mutagenic.
Describe Invasion and Metastasis
●Normal cells maintain their location in the body and generally do not migrate
●The movement of cancer cells to other parts of the body is a major cause of cancer deaths
●Alterations of the genome may affect the activity and/or levels of enzymes involved in invasion or molecules involved in cell-cell or cellular-extracellular adhesion
Describe Angiogenesis
●Normal cells depend on blood vessels to supply oxygen and nutrients but the vascular architecture is more or less constant in the adult
●Cancer cells induce angiogenesis, the growth of new blood vessels, needed for tumor survival and expansion
●Altering the balance between angiogenic inducers and inhibitors can activate the angiogenic switch.
Describe Genomic Instability and Mutation
●Acquiring the core hallmarks of cancer usually depends on genomic alterations
●Faulty DNA repair pathways can contribute to genomic instability
Describe Evasion of Cell Death
●Normal cells are removed by apoptosis, often in response to DNA damage
●Cancer cells evade apoptotic signals
Describe Reprograming of Energy Metabolism
●Uncontrolled cell division demands increases in fuel and biosynthetic precursors that is obtained by adjusting energy metabolism
●Unlike normal cells, cancer cells carry out glycolysis even in the presence of oxygen. Glycolysis intermediates can be used in biosynthetic pathways.
Describe the process a new cancer drug undergoes to receive FDA approval.
●PreClinical Trials
In vitro
Cell culture
In vivo
Animal testing
●Clinical Trials
●Human trials
Phase 0
Phase I
Phase II
Phase III
Phase IV
Explain how uvB causes mutations that can cause cancer.
Damage by UVB
•Pyrimidone Photoproducts
Mimics an abasic site
Relatively easily repaired
•Cyclobutane pyrimidine dimers
20X to 40X more prevalent than pyrimidone photoproducts
More difficult to repair accurately
Errors in DNA synthesis if not repaired
Causes a bend in the DNA that blocks accurate reading by DNA Polymerase
DNA polymerase incorporates A residues
Explain how ionizing radiation causes mutations that can cause cancer.
Any radiation process in which the individual quanta of radiated energy are able to ionize atoms or molecules of the substance in which the energy is absorbed. This leads to chemical changes that can damage biological tissues and structural materials
•Likely to cause mutations by creating ions that can lead to damaged DNA
•Produces reactive oxygen species when interacting with water (most likely molecule for ionizing radiation to damage)
Explain how four different types of chemical carcinogens increase the risk of acquiring cancer.
•Polycyclic aromatic hydrocarbons (PAHs)
•Addition of rings and/or methyl groups into the bay region of three aromatic rings converts the chemicals to carcinogens
Ex Benzopyrene conversion to benzopyrene diol epoxides by P450 enzymes
•Aromatic Amines
•HCAs (heterocyclic amines) are formed when amino acids, sugars, and creatine (a substance found in muscle) react at high temperatures.
•Ex fried hamburgers or steaks
•Nitrosamines and Nitrosamides
•Found in tobacco
•Formed when preservative nitrates react with amines in fish and meats during smoking
•Alkylating Agents (Aldehydes and Phenolics)
•Mustard Gas
•Forms intra-chain and inter-chain crosslinks in DNA
