Hosam Mohamed-
sustain proliferative signaling, evade growth suppressors, resisting apoptosis, replicative immortality, angiogenesis, invasion/metastasis
What are the 6 hallmarks of cancer cells?
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a
What hallmark does Ras mutations belong to?
a) sustain proliferative signaling
b) replicative immortality
c) resisting cell death
d) inducing angiogenesis
e) invasion/metastasis
f) evading growth suppressors
-
s-phase; causes cell to undergo dna synthesis when it should abort and undergo apoptosis
Ras commits cell to what phase of cell cycle ? What implication does this present?
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H, K, N
What are the 3 different Ras proteins?
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c
Which Ras mutation is most prevalent in Pancreatic cancers?
A) HRAS
B) NRAS
C) KRAS
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cetuximab; panitumumab; wild type
____________ & ____________ prevent ligand binding and deactivate EGFR signaling in _________ KRAS
-
KRAS G12C
-most frequent KRAS mutation
-locks KRAS protein in activated state leading to increased cellular signaling and unchecked tumor growth
- no therapeutic efficacy with monoclonal antibodies
-
LUMAKRAS (Sotorasib)
-designed to inhibit mutant KRAS G12C without affecting wild-type KRAS
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kras g12c mutations in locally advanced or metastatic non-small cell lung cancer
Who is indicated for Lumakras?
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Retinoblastoma suppressor (Rb)
-tumor suppressor protein that acts to control whether cells enter G1 or stay in safer resting state
-
b
Which protein is referred to as a checkpoint protein/ gene?
a) KRAS
b) Rb
c) EGFR
d) Bcl-2
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G0
-resting phase where the cell has left the cycle and has stopped dividing
-
G1
-cell size increases
-checkpoint that ensures that cell is ready for DNA synthesis
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S phase
-phase where dna replication occurs
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G2
-gap between DNA synthesis and Mitosis
-cell continues to grow
-ensures everything is good before cell divides
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M
-cell growth stops
-cellular energy is focused on dividing into 2 daughter cells
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bind to and inactivate E2F transcription factors
What is the primary function of Rb?
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hyper-phosphorylation; CDK/cyclin
In cancer cells, _______ of Rb by _______ inactivates Rb, and gene expression is turned on.
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palbociclib; HR+ and HER2- metastatic brest cancer; selective inhibitor of CDK 4/6
Ibrance
-generic
-indication
-moa
-
apoptotic trigger; Bcl-2
The ___________ is controlled by counterbalancing pro- and anti-apoptotic proteins of the _________ family of regulatory proteins.
-
Bax & Bak
-apoptotic triggering proteins that are embedded in outer mitochondrial membrane
-
disrupt integrity of outer mitochondrial membrane, form oligomeric complexes with BH3- only proteins creating pores in the mitochondria that release pro-apoptotic signaling proteins
What happens when Bax & Bak are relieved of inhibition?
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cytochrome c
-most important pro-apoptotic signaling protein
-
activates cascade of caspases (proteolytic enzymes) that start the apoptotic process
Cytochrome C function?
-
BH3 mimetics
-drive cancer tells toward apoptosis
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VENCLEXTA (ventoclax)
-promotes pore formation and apoptotic cell death by binding to Bcl-2, causing it to dissociate from BH3-only proteins
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17p deletion; TP53 tumor suppressor
Approximately 10% of patients with untreated Chronic lymphocytic leukemia and 20% of patients with relapsed CLL carry a ______. This involves the loss of _________ gene.
-
loss of telomerase activity
Senescene is caused by
-
Telomere
-repeating sequence of double-stranded DNA located at the ends of chromosomes
-each time cell divides; telomere length shortens
-
Telomerase
-a reverse transcriptase that lengthens telomeres by adding on repeating sequences of DNA by using a hairpin RNA as a template
-
c
Telomerase activity is a hallmark in over ______ of cancers.
a) 25%
b) 75%
c) 90%
d) 50%
-
normal tissue; reactivating
Tumors usually have shorter telomeres than _______. Telomerase works against this by ________ telomere growth.
-
bevacizumab, metastatic colorectal cancer, inhibits angiogenic factors, GI perforation, hemorrhage, wound healing issues
AVASTIN
- generic
- indication
-MOA
-BBW
-
overt metastasis; metastatic cascade
__________ is the final manifestation of a series of events collectively known as the ____________.
-
cabozantinib, medullary thyroid cancer, inhibits HGF/c-Met pathway and VEGFR2), CYP3A4, GI perforations; hemorrhage
COMETRIQ
-generic
-indication
-MOA
-Metabolism
-BBW
-
f
What hallmark does the Rb protein belong to?
a) sustain proliferative signaling
b) replicative immortality
c) resisting cell death
d) inducing angiogenesis
e) invasion/metastasis
f) evading growth suppressors
-
b
What hallmark does telomerase belong to?
a) sustain proliferative signaling
b) replicative immortality
c) resisting cell death
d) inducing angiogenesis
e) invasion/metastasis
f) evading growth suppressors
-
c
What hallmark does Bcl-2 belong to?
a) sustain proliferative signaling
b) replicative immortality
c) resisting cell death
d) inducing angiogenesis
e) invasion/metastasis
f) evading growth suppressors
-
d
What hallmark does Bevacizumab (AVASTIN) work against?
a) sustain proliferative signaling
b) replicative immortality
c) resisting cell death
d) inducing angiogenesis
e) invasion/metastasis
f) evading growth suppressors
-
e
What hallmark does Cabozantinib (COMETRIQ) work against?
a) sustain proliferative signaling
b) replicative immortality
c) resisting cell death
d) inducing angiogenesis
e) invasion/metastasis
f) evading growth suppressors
