BIO 302 - Exam 2 - Childhood Cancer & The (Evolutionary) Theory of Cancer PowerPoints

Question 1

T/F: there is no prevention for childhood cancers.

Answer 1

True.

Question 2

______ is the leading cause of death in the 1-44 age group.
______ is now the 2nd leading cause of death for the 1-44 age group.

______ remains in the top 5 causes of death for the 1-44 age group.
Cancer is the #1 _____ _____ of children in the U.S.

Answer 2

Unintentional injury.
Suicide.
Homicide.
disease killer.

Question 3

About _____ now survive 5 years
About _____ of survivors die prematurely due to their original cancer, a secondary cancer or other effects of treatment
Long-term survival is _____ - survival long term: you carry morbidity from the treatment for the rest of your life.

Almost all (_____) develop chronic health conditions related to the cancer or the treatment.

Answer 3

80%. 20%. 66%.98%.

Question 4

The cause of most pediatric cancers is ________.

Answer 4

UNKNOWN

Question 5

MOST COMMON CHILDHOOD CANCERS

Answer 5

ACUTE LEUKEMIA 30%
BRAIN AND SPINAL CORD 26%
NEUROBLASTOMA 6%
WILMS TUMOR 5%
LYMPHOMAS
HODGKIN LYMPHOMA 3%
NON-HODGKIN LYMPHOMA 5%
RHABDOMYOSARCOMA 3%
BONE 3%
RETINOBLASTOMA 2%

Question 6

The childhood leukemias are acute leukemias.

Acute myelogenous leukemia (AML)
Acute lymphocytic leukemia (ALL)
Chronic myelogenous leukemia (CML)
Chronic lymphocytic leukemia (CLL)

Answer 6

(AML): occur in both children and adults
(ALL): most common type of leukemia in children. Also affects adults.
(CML): mainly affects adults.
(CLL): most often over the age of 55.

Question 7

Malignant clonal proliferation of mutated precursor cells with reduced capacity to differentiate (cell division at the expense of differentiation)
Myeloid precursors: acute myelogenous leukemia (AML)
Lymphoid precursors: acute lymphocytic leukemia (ALL)
Maturation arrest occurs at an immature (“blast”) stage
In chronic leukemia, arrest occurs at a more mature stage of development
Blast cells don’t mature, don’t function normally, and don’t die
Normal bone marrow becomes completely replaced by blast cells
Bone marrow suppression ensues causing:
Anemia
Immunosuppression and infection
Thrombocytopenia (low platelets → clotting problems → hemorrhage)

Question 8

What is Peto’s Paradox?

Answer 8

The lack of correlation between body size and cancer risk is known as Peto’s Paradox.

Question 9

Define the 3 phases of clinical trials.

Answer 9

Phase I Clinical Trial
* maximum tolerated dose
Phase II Clinical Trial
* hint of effectiveness
Phase III Clinical Trial
* randomized, placebo controlled
test of effectiveness
(expensive!)
* “success” = extend life by an
average of a few months

Question 10

The more drug - the stronger the effect (dose-response curve).

What is the therapeutic index?

Answer 10

Space between the therapeutic effect and the topic effect.

Question 11

The Malevolence of Cancer: Why are these phenotypes universal across cancers?

Answer 11

• Generates own proliferation
  signals
• Ignores anti-growth signals
• Disables programmed cell death
• Can divide indefinitely
• Increases mutation rates
• Escapes immune system
• Angiogenesis
• Metastasis

Question 12

What are the Necessary and Sufficient Conditions of how tumors Evolve by Natural Selection?

Answer 12

Fuel: Variation in the population
* Somatic genetic alterations
Traction: Variation is heritable
* Alterations in DNA and methylation
Engine: Variation affects reproduction and survival
* Suppression of apoptosis, etc.

Question 13

Universal biomarkers
We should measure the process of somatic evolution using what 5 things?

MR
PS
GT
RCE
H

Answer 13

(1) Mutation rate
(2) Population size
more cells = more chances for mutations
(3) Generation time
more cell divisions = more mutations
(4) Rate of clonal expansion
(strength of selection)
faster expansion = larger target population for next mutation
(5) Heritability

Question 14

Lessons from Pest Management

Answer 14

(1) Assume resistance is present
(2) Do not treat if the damage is tolerable
(3) Use the minimum effective dose
(4) Diversify the modes of action as much as possible

(5) Never use the same mode of action twice in a row
(separate re-applications in time as much as possible)
(6) Combine chemical controls with mechanical, biological and cultural controls
(7) Maintain sensitive pests to compete with resistant pests
(8) Monitor continuously and adapt

Question 15

How does Standard (Maximum Tolerated Dose) Therapy work?

Answer 15

Oncologists kill Sensitive Cells resulting in Resistant Cells

Question 16

How does adaptive therapy work?

Answer 16

Oncologists control Sensitive Cells control Resistant Cells

Question 17

Huge unrealized opportunities

Answer 17

• Prevent cancer and therapeutic resistance by slowing the
  somatic evolutionary process
• Measure the parameters of evolution for prediction/
  prognosis
• Reconstruct the order of mutations from cell phylogenies
• Comparative oncology: why don’t elephants and whales
  get more cancer?
  Kostadinov

Question 18

Huge unrealized opportunities

Answer 18

• Identify and target the mechanisms of therapeutic resistance
• Pre-select against therapeutic resistance (“the sucker’s gambit”)
• Prevent cancer by selecting for the benign state (“benign cell boosters”)
• Prevent cancer mortality by
• Using sensitive cells to control resistance (adaptive therapy)
• Selecting against the lethal clones
• Intervening in the proximal cause of death
• Treat to extend life, not to kill cancer cells!