Description
BIO 302 Exam 2 Study Guide
Dr. Compton
Week 6: The Evolutionary Theory of Cancer
1. Theory Is a Framework For Organizing Information and Making Predictions a. One starting 3 billion years ago
b. One starting in the 1960s
c. One that starts every day and plays out over decades
2. The Multicellular Covenant
a. Cells of our bodies and somatic cells curtail their reproduction
b. Sperm and egg cells propagate the genes
c. Cancer is the breaking of that covenant
3. Story of a Cancer
a. Chapter 1: in the beginning…
i. Normal cells divide
ii. Copying 3 billion base pairs
iii. No copying procedure is perfect
iv. You can make it worse: smoking, UV light, chronic inflammation v. Mutation in a tumor suppressor gene
b. Chapter 2: being fruitful and multiplying
i. A descendant of the founding mother acquires another mutation ii. Generates its own growth signal
iii. Leads to clonal expression We also discuss several other topics like webassign sucks
c. Chapter 3: attempted suicide averted
i. Misbehaving cells told to commit suicide
ii. Apoptosis
d. Chapter 4: fat, cheap, and out of control
i. Multiple layers of error checking
ii. If few mutations, the cell pauses to fix them
iii. Too many mutations trigger programmed cell death
e. Chapter 5: the fountain of youth
i. Every time a cell divides, telomeres shorten
1. Limits number of times out cells can divide= aging
ii. Mutation that turns on telomerase- rebuilding its telomeres iii. Immortality
f. Chapter 6: dying of thirst and building of aqueducts
i. Oxygen and glucose can only diffuse so far We also discuss several other topics like hist 103
ii. angiogenesis
g. Chapter 7: camouflage and guerrilla war
i. Tumors may start producing so much mutated protein that the immune system recognized them as foreign
ii. Slaughter ensues
h. Chapter 8: new voyages of discovery
i. Millions of cells have the primary tumor
ii. Invasion into neighboring organs
i. Chapter 9: the phoenix and the scourge
i. Most chemotherapies attempt to kill all proliferating cells in the body ii. Normal proliferating cells die too Don't forget about the age old question of chuscle
We also discuss several other topics like nadja rhodes
iii. Devastating scourge for the tumor cells
j. Chapter 10: the end environmental catastrophe
i. When tumor regrows, it derives from resistant ancestros so therapy is ineffective
ii. Eventually tumor cells so devastate their environment that the host dies 4. Necessary and Sufficient Conditions for Natural Selection
a. Fuel: variation in the population
b. Traction: variation is heritable
c. Engine: variation affects reproduction and survival
5. Early Diagnosis and Overdiagnosis
a. Metastatic cancer is hard to cure
b. So focus on early detection and prevention We also discuss several other topics like rels 1000 class notes
c. Screening preferentially identifies slow growing tumors
d. Need “biomarkers” to distinguish lethal tumors from irrelevant tumors 6. Universal Biomarkers
a. We should measure the process of somatic evolution:
i. Mutation rate
ii. Population size
iii. Generation time
iv. Rate of clonal expansion
Week 6: Cancer As A Complex Adaptive System:
1. Complicated Systems: Low Degrees of Design Freedom
a. Behavior of components and the assembled whole system is predictable b. Calculable tolerance limits and likely failure points
c. Performance of system fixed and not capable of autonomous evolution 2. Dynamic Complex (Adaptive) Systems
a. Exhibit behaviors created by constantly changing patterns of interactions between the components of the system
3. Evolvability and Emergence: The Hallmarks of Complex Systems We also discuss several other topics like psyc1001
a. New properties emerge from the interactions of simpler units
b. Properties of the whole system cannot be reliably predicted from knowledge of the properties of the simplerr isolated component units
4. The Biological Complexity Of Cancer And The Design Of Treatment Strategies a. Successful surgical removal of primary before metastatic spread tumor b. Targeting metastatic disease and circumventing Rx resistance
5. Cancer As A Complex Adaptive System
a. Cancer is a multi-component, ecosystem involving complex interactions between cancer cells and host systems over extended time periods
b. Genotoxic insults, mutations and genomic instability are drivers of cancer initiation and progression
c. Evolution of genomic and phenotypic diversity is relentless
d. Adaptive evolution of tumor cell clones to diverse selection pressures occurs e. Clonal heterogeneity and phenotypic diversification pose formidable challenges for successful treatment
Week 7: Cancer Epidemiology and Prevention:
1. Cancer Statistics
a. Cancer incidence and mortality:
i. Vary by body site location
ii. Vary by geographic region
iii. Vary by human behavior patterns
2. Medicine and Saving Lives
a. What is the goal of the society and medicine with regard to death?
i. Quantity of life
1. Easier to measure
2. Objective
ii. Quality of life
a. Harder to measure
b. Subjective
3. What Happened in the 20th Century to Increase Life Expectancy? a. Public health
b. Antibiotics
c. Vaccines
d. Cardio-pulmonary resuscitation
e. Chemotherapy
f. Ventilator
g. Prevention of heart disease and against smoking
4. Where Does Cancer Data Come From?
a. In the U.S. data is collected on every cancer patient
i. SEER
ii. CDC
iii. NAACR
iv. SEER-Medicare Linked Database
v. The National Cancer Data Base of the Commission on Cancer 5. Acute Leukemia
a. A malignant clonal expansion of precursor cells with reduced capacity to differentiate
b. Maturation arrest occurs at the blast stage
c. Cells don’t mature, don’t function normally, and don’t die
d. Normal bone marrow becomes completely replaced by blast cells 6. Pediatric Cancer: A Snapshot
a. Cancer is the #1 disease killer of children in the US
b. Cancer kills more children than every other pediatric disease COMBINED c. The cause is unknown
7. The Importance of Value
a. Some preventive measures save money, while others do not, although they may still be worthwhile because they confer substantial health benefits relative to their cost
b. Value means that money is saved relative to competing options
8. Take Home Messages
a. Incidence and mortality stats are labor intensive and expensive to accrue but of incomparable value for monitoring and prevention
b. Cancer results from a combination of host factors and environmental factors c. Most cancer can be prevented by avoiding cancer fostering factors, adopting cancer inhibiting behaviors, getting vaccinated and getting screened
d. Prevention is always preferable to therapy, even if a cure can be achieved with therapy
Week 8: Fundamental and Goals of Cancer Screening and Detection 1. Fundamentals
a. Cancer patient management is guided by the following principles:
i. The earlier the cancer is discovered and effectively treated, the better the outcome for most cancers, but there are exceptions
ii. Right therapy and management are dependent on right diagnosis and assessment
iii. All cancer therapies have undesirable effects: the goal is to have desirable effects outweigh undesirable effects
2. Find It Early: Screening
a. Screening for cancer involves:
i. Testing people without symptoms
ii. Testing defined populations
b. For most cancers there are no effective screening tests
3. Why Screen For Cancer?
a. Cancer is a common disease
b. Pre-clinical phases of cancer can be long
c. Cancer in late state can be lethal and treatment of advanced cancer is not very effective overall
d. Effective screening to find and treat cancer or pre-cancers at early stages of development can save lives or some cancer types
4. Test Characteristics
a. Test sensitivity: a test’s ability to correctly identify those with the disease b. Test specificity: a test’s ability to correctly identify those without the disease 5. Predictive Value of Screening Tests
a. Positive predictive value: probability that those with a positive test actually have the disease
b. Negative predictive value: the probability that those with a negative test don’t have the disease
6. Our Most Effective Screening Tools
a. Pap smear
b. Colonoscopy
c. Low-dose computed tomography
7. Screening That Saves Lives From The Specific Cancer:
a. Cervical cancer
b. Colon and rectal cancer
8. Take Home Messages
a. Goal of screening is to detect disease early and treat before cancer has progressed b. Effective screening is defined by a decrease mortality from cancer in the screened vs. unscreened population
c. It’s ineffective if it does not decrease mortality
d. Benefit-to-harm ratio of screening using a particular test depends on false negative and false positive rates
e. Utility of a screening test depends on its predictive value and prevalence of the disease
Week 10-11: Cancer Detection, Diagnosis, Assessment, and Prognosis 1. Diagnosis
a. Assessment of a person with symptoms
b. Identification of the problem through a process of evaluation 2. Actions in the Cancer Work-Up
a. Physical examination
b. Procedures
c. Clinical imaging
d. cell/tissue sampling
e. Blood tests
3. Radiological Assessment
a. Masses are detected
b. Small tumors may be missed
4. Techniques Using Ionizing Radiation
a. Mammography
b. X-ray
c. CT scan
5. Techniques Using Radioactive Isotopes
a. Nuclear medicine scans
b. PET scans
6. Technique Without Ionizing Radiation
a. MRI
b. Ultrasonography
7. Pathological Diagnosis
a. No meat, no treat
i. Standard of care: tissue is the issue
8. Fundamental of Cancer Evaluation
a. Stage-how much cancer is present
i. How far cancer has progressed at diagnosis based on extent of local tumor and spread of disease
b. The greater the spread, the higher the stage
9. Stage: Overview
a. Stage 0: early form
b. Stage 1: localized
c. Stage 2: early locally advanced
d. Stage 3: late locally advanced
e. Stage 4: metastasized
10. What is Prognosis?
a. Estimation of a future event: prediction of survival after diagnosis and primary treatment
b. Diagnosis is the identification of a condition
c. Prognosis is a future prediction
11. Molecular Testing for Cancers
a. Done for 3 main reasons:
i. Diagnosis
ii. Prognosis
iii. Prediction of response to therapy
12. Take Home Messages
a. Correct diagnosis is essential for accurate prognosis and correct treatment b. Symptoms and signs of cancer may point to the site/source of cancer but may be non-specific
c. Imaging studies primary basis for establishing clinical stage of tumor d. Prognosis is influenced by factors related to tumor, the patient, and the medical environment
e. Dominant prognostic factor for the majority of carcinomas is stage f. Multidisciplinary teams required for best cancer car
***END OF STUDY GUIDE***