GMS 6540 Cancer Exam Questions With
Complete Answers
What causes a cancer cell to go rogue? - ANSWER chemicals, virus, radiation
What are the steps when a cancer goes rogue? - ANSWER 1) normal cell then a
genetic change to initiated cell.
2) initiated cell then selective clonal expansion to pre-neoplastic lesion.
3) Pre-neoplastic lesion then genetic change to malignant tumor
4) Malignant tumor then genetic change to clinical cancer
5) clinical cancer then genetic change to cancer metastasis
Hallmark #1 - ANSWER Self-Sufficiency in Growth Signals
Hallmark #1 means - ANSWER Self-Sufficiency in Growth Signals
Cell growth is normally tightly regulated, requiring a pro-growth signal.
Cancer cells bypass this requirement in a number of ways
How does cell signaling work? - ANSWER Pro-growth molecule (ligand) binds to
extracellular domain
Intracellular domain becomes active
Signaling cascade proceeds
Pro-growth proteins are transcribed
How do cancer cells become self-sufficient? - ANSWER Abnormal ligand
production, autocrine (self) signaling
Induced paracrine (external) signaling
Upregulated receptor levels
Mutation-induced constitutive signaling
Hallmark #2 - ANSWER Insensitivity to Anti-Growth Signals
Normal cells need to overcome anti-growth signals in order to divide
,Anti-growth signals can be both normal and/or induced
Anti-growth signals can originate either internally or externally
Hallmark #3 - ANSWER Unstable DNA
This is an "enabling" hallmark
Required for tumor progression
Can lead to drug resistance
If DNA became stable, the tumor would survive
Two main forms of DNA instability: Genetic Instability and Chromosomal
Instability
Hallmark #4: - ANSWER Metastasis
The transmission of cancer cells from the original site to one or more sites
elsewhere in the body by the way of blood vessels or lymphatics
Hallmark #5 - ANSWER Evasion of Apoptosis
Apoptosis is a cell SUICIDE mechanism.
Its hallmarks are:
Cell volume loss
Membrane blebbing and formation of apoptotic bodies, DNA fragmentation and
condensation, Cytoskeleton collapse, Engulfment by immune cells, Non-
inflammatory
Hallmark #6 - ANSWER Abnormal Cellular Metabolism
• Most mammalian cells under normoxic conditions pursue oxidative
phosphorylation of glucose.
OXPHOS = 38 molecules of ATP/molecule of glucose.
Cancer cells in contrast metabolize glucose through glycolysis.
Glycolysis = 2 molecules of ATP/ molecule of glucose.
Phenomena of aerobic glycolysis in cancer cells was first observed by Nobel
Prize winner Otto Warburg
• Warburg Effect
Hallmark #7 - ANSWER Angiogenesis
, Angiogenesis occurs when there is an imbalance: the angiogenic switch
Hallmark #8 - ANSWER Inflammation
Hallmark #9 - ANSWER Evasion of the Immune System
Hallmark #10 - ANSWER Immortality
Antimetabolites - ANSWER 5-FU, Methotrexate
S phase: DNA synthesis
Phase-nonspecific drugs - ANSWER Active on cells in all phases of the cell
cycle:
alkylating agents (cyclophosphamide)
cross-linkers (cysplatin)
topoisomerase inhibitors (doxorubicin)
Phase-specific drugs - ANSWER Microtubule drugs(paclitaxel,vincristine)
Gompertzian growth - ANSWER Relationship between growth fraction and drug
action
Hemorrhagic cystitis - ANSWER Cyclophosphamide (Cytoxan®)
Neurotoxicity - ANSWER microtubule inhibitors (i.e., vincristine, paclitaxel)
Cisplatin
Cardiotoxicity - ANSWER Doxorubicin
Pulmonary fibrosis - ANSWER Bleomycin
Topo II inhibitor - ANSWER Doxorubicin
Microtubule inhibitor - ANSWER Vincristine
DHFR (Dihydrofolate reductase) inhibitor - ANSWER Methotrexate
DNA cross-linking drug - ANSWER Mephalan, cisplatin
COMBINATION CHEMOTHERAPY:GOLDIE-COLDMAN HYPOTHESIS - ANSWER
Hypothesis: The frequency of drug resistance is related to the intrinsic mutation
rate
Tumors have a higher intrinsic mutation rate (increased genetic instability)
relative to normal proliferating cells
Complete Answers
What causes a cancer cell to go rogue? - ANSWER chemicals, virus, radiation
What are the steps when a cancer goes rogue? - ANSWER 1) normal cell then a
genetic change to initiated cell.
2) initiated cell then selective clonal expansion to pre-neoplastic lesion.
3) Pre-neoplastic lesion then genetic change to malignant tumor
4) Malignant tumor then genetic change to clinical cancer
5) clinical cancer then genetic change to cancer metastasis
Hallmark #1 - ANSWER Self-Sufficiency in Growth Signals
Hallmark #1 means - ANSWER Self-Sufficiency in Growth Signals
Cell growth is normally tightly regulated, requiring a pro-growth signal.
Cancer cells bypass this requirement in a number of ways
How does cell signaling work? - ANSWER Pro-growth molecule (ligand) binds to
extracellular domain
Intracellular domain becomes active
Signaling cascade proceeds
Pro-growth proteins are transcribed
How do cancer cells become self-sufficient? - ANSWER Abnormal ligand
production, autocrine (self) signaling
Induced paracrine (external) signaling
Upregulated receptor levels
Mutation-induced constitutive signaling
Hallmark #2 - ANSWER Insensitivity to Anti-Growth Signals
Normal cells need to overcome anti-growth signals in order to divide
,Anti-growth signals can be both normal and/or induced
Anti-growth signals can originate either internally or externally
Hallmark #3 - ANSWER Unstable DNA
This is an "enabling" hallmark
Required for tumor progression
Can lead to drug resistance
If DNA became stable, the tumor would survive
Two main forms of DNA instability: Genetic Instability and Chromosomal
Instability
Hallmark #4: - ANSWER Metastasis
The transmission of cancer cells from the original site to one or more sites
elsewhere in the body by the way of blood vessels or lymphatics
Hallmark #5 - ANSWER Evasion of Apoptosis
Apoptosis is a cell SUICIDE mechanism.
Its hallmarks are:
Cell volume loss
Membrane blebbing and formation of apoptotic bodies, DNA fragmentation and
condensation, Cytoskeleton collapse, Engulfment by immune cells, Non-
inflammatory
Hallmark #6 - ANSWER Abnormal Cellular Metabolism
• Most mammalian cells under normoxic conditions pursue oxidative
phosphorylation of glucose.
OXPHOS = 38 molecules of ATP/molecule of glucose.
Cancer cells in contrast metabolize glucose through glycolysis.
Glycolysis = 2 molecules of ATP/ molecule of glucose.
Phenomena of aerobic glycolysis in cancer cells was first observed by Nobel
Prize winner Otto Warburg
• Warburg Effect
Hallmark #7 - ANSWER Angiogenesis
, Angiogenesis occurs when there is an imbalance: the angiogenic switch
Hallmark #8 - ANSWER Inflammation
Hallmark #9 - ANSWER Evasion of the Immune System
Hallmark #10 - ANSWER Immortality
Antimetabolites - ANSWER 5-FU, Methotrexate
S phase: DNA synthesis
Phase-nonspecific drugs - ANSWER Active on cells in all phases of the cell
cycle:
alkylating agents (cyclophosphamide)
cross-linkers (cysplatin)
topoisomerase inhibitors (doxorubicin)
Phase-specific drugs - ANSWER Microtubule drugs(paclitaxel,vincristine)
Gompertzian growth - ANSWER Relationship between growth fraction and drug
action
Hemorrhagic cystitis - ANSWER Cyclophosphamide (Cytoxan®)
Neurotoxicity - ANSWER microtubule inhibitors (i.e., vincristine, paclitaxel)
Cisplatin
Cardiotoxicity - ANSWER Doxorubicin
Pulmonary fibrosis - ANSWER Bleomycin
Topo II inhibitor - ANSWER Doxorubicin
Microtubule inhibitor - ANSWER Vincristine
DHFR (Dihydrofolate reductase) inhibitor - ANSWER Methotrexate
DNA cross-linking drug - ANSWER Mephalan, cisplatin
COMBINATION CHEMOTHERAPY:GOLDIE-COLDMAN HYPOTHESIS - ANSWER
Hypothesis: The frequency of drug resistance is related to the intrinsic mutation
rate
Tumors have a higher intrinsic mutation rate (increased genetic instability)
relative to normal proliferating cells
