Cancer Biology AI Flashcards
(482 cards)
1
Q
What is signal transduction?
A
The process by which a cell converts one kind of signal or stimulus into another.
2
Q
What is a receptor tyrosine kinase (RTK)?
A
A type of cell surface receptor that activates intracellular signaling pathways when bound by a ligand.
3
Q
What happens when an RTK is activated?
A
It undergoes dimerization and autophosphorylation, initiating downstream signaling cascades.
4
Q
What are second messengers?
A
Molecules like cAMP, IP3, or Ca2+ that relay signals from receptors to target molecules inside the cell.
5
Q
Which protein acts as a molecular switch in the MAPK pathway?
A
Ras, a small GTPase.
6
Q
What is the order of key signaling proteins in the Ras/MAPK pathway?
A
RTK → Grb2/SOS → Ras → Raf → MEK → ERK.
7
Q
What does ERK do in the MAPK pathway?
A
It translocates to the nucleus to activate transcription factors and promote cell proliferation.
8
Q
How is Ras inactivated?
A
By hydrolyzing GTP to GDP, often facilitated by GTPase-activating proteins (GAPs).
9
Q
What is the role of PI3K in cancer signaling?
A
It phosphorylates PIP2 to PIP3, activating the Akt signaling pathway.
10
Q
What does activated Akt promote?
A
Cell survival, growth, and metabolism.
11
Q
What is the function of PTEN?
A
It dephosphorylates PIP3 to PIP2, negatively regulating the PI3K/Akt pathway.
12
Q
How is the PI3K pathway activated?
A
Through RTK or GPCR signaling leading to PI3K recruitment and activation.
13
Q
What triggers the JAK/STAT pathway?
A
Cytokine binding to their receptors, activating associated JAKs.
14
Q
What is the function of STAT proteins?
A
They are transcription factors that translocate to the nucleus to activate gene expression.
15
Q
How is the JAK/STAT pathway negatively regulated?
A
By SOCS proteins and phosphatases that inhibit signaling.
16
Q
How can RTKs become oncogenic?
A
By gene amplification, point mutation, or chromosomal rearrangements leading to constitutive activation.
17
Q
What is HER2 and why is it significant in cancer?
A
HER2 is an RTK overexpressed in certain breast cancers, associated with aggressive disease.
18
Q
What is EGFR and how is it targeted in cancer?
A
EGFR is a key RTK often mutated or overexpressed in cancers; it can be targeted by tyrosine kinase inhibitors like gefitinib.
19
Q
What is a fusion protein involving signaling pathways often seen in leukemia?
A
BCR-ABL fusion protein in chronic myeloid leukemia activates constitutive tyrosine kinase activity.
20
Q
What type of drug is imatinib?
A
A tyrosine kinase inhibitor that targets BCR-ABL in CML.
21
Q
How do MEK inhibitors work?
A
They block MEK activity in the MAPK pathway to inhibit proliferation.
22
Q
Why is targeting downstream pathways useful in cancer?
A
Because mutations upstream (e.g., in Ras or RTKs) can lead to constitutive signaling.
23
Q
What is crosstalk in cell signaling?
A
Interaction between different signaling pathways that can modulate the final cellular response.
24
Q
What is feedback inhibition in signaling?
A
A process where downstream products inhibit upstream components to prevent overactivation.
25
What are scaffold proteins and their role in MAPK pathway?
They organize signaling components and enhance specificity and efficiency.
26
How is Akt linked to metabolism?
Akt activates mTOR and influences glucose uptake and protein synthesis.
27
Why are signaling pathways often redundant in cancer?
To ensure survival and adaptability, tumors often activate multiple overlapping pathways.
28
What is the clinical significance of PI3K mutations?
PI3K mutations are common in many cancers and are being targeted by isoform-specific inhibitors.
29
What is apoptosis?
A form of programmed cell death that occurs in multicellular organisms to remove damaged or unnecessary cells.
30
How is apoptosis different from necrosis?
Apoptosis is a regulated, clean process while necrosis is unregulated and causes inflammation.
31
What are the two main pathways of apoptosis?
Intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways.
32
What triggers the intrinsic pathway of apoptosis?
Internal stress signals such as DNA damage, hypoxia, or growth factor deprivation.
33
What triggers the extrinsic pathway of apoptosis?
External signals like FasL or TNFα binding to death receptors on the cell surface.
34
What are caspases?
Cysteine proteases that cleave proteins to initiate and execute apoptosis.
35
What are initiator caspases?
Caspases such as caspase-8 and caspase-9 that respond to apoptotic signals and activate effector caspases.
36
What are executioner caspases?
Caspases such as caspase-3, -6, and -7 that carry out the dismantling of the cell.
37
Which organelle is central to intrinsic apoptosis?
The mitochondrion.
38
What is the function of cytochrome c in apoptosis?
It is released from mitochondria and helps form the apoptosome.
39
What is the apoptosome?
A multi-protein complex composed of cytochrome c, APAF1, and caspase-9 that activates apoptosis.
40
What is the role of Bcl-2 in apoptosis?
It inhibits apoptosis by preventing mitochondrial membrane permeabilization.
41
What do BAX and BAK do?
They promote apoptosis by forming pores in the mitochondrial membrane.
42
What is BID and how does it function?
BID is a BH3-only protein that links the extrinsic and intrinsic apoptotic pathways.
43
What are death receptors?
Receptors like Fas (CD95) and TNFR1 that initiate apoptosis upon ligand binding.
44
What complex is formed during extrinsic apoptosis?
The death-inducing signaling complex (DISC).
45
Which caspase is activated in the extrinsic pathway?
Caspase-8.
46
How do cancer cells evade apoptosis?
By overexpressing anti-apoptotic proteins (e.g., Bcl-2), losing pro-apoptotic factors, or mutating p53.
47
What is the role of p53 in apoptosis?
It promotes apoptosis in response to DNA damage by upregulating BAX, NOXA, and PUMA.
48
What is anoikis?
A form of apoptosis triggered by detachment from the extracellular matrix.
49
What are BH3 mimetics?
Drugs that mimic pro-apoptotic BH3-only proteins to inhibit Bcl-2 and trigger apoptosis.
50
What is TRAIL?
TNF-related apoptosis-inducing ligand that can selectively induce apoptosis in cancer cells via death receptors.
51
What is the main limitation of TRAIL-based therapies?
Resistance due to mutations or loss of death receptors.
52
What is oblimersen?
An antisense oligonucleotide that targets Bcl-2 mRNA to reduce its expression.
53
What is mitochondrial outer membrane permeabilization (MOMP)?
A critical step in intrinsic apoptosis where BAX/BAK form pores in mitochondria.
54
How does SMAC/DIABLO promote apoptosis?
By inhibiting IAPs (inhibitor of apoptosis proteins), thus allowing caspase activity.
55
What are IAPs and their role?
Inhibitor of apoptosis proteins that prevent caspase activation.
56
How does FLIP protein affect extrinsic apoptosis?
It inhibits caspase-8 activation, blocking the death receptor pathway.
57
What is the role of NOXA and PUMA?
They are pro-apoptotic proteins induced by p53 and promote mitochondrial apoptosis.
58
What is the function of APAF1?
It forms the apoptosome by binding cytochrome c and procaspase-9.
59
What are IAPs and how are they regulated?
Inhibitor of apoptosis proteins block caspase activity and are counteracted by SMAC/DIABLO.
60
What cancer types show high Bcl-2 expression?
Follicular lymphoma, chronic lymphocytic leukemia, and some solid tumors.
61
What are decoy receptors in the context of TRAIL?
Receptors that bind TRAIL but lack death domains, preventing apoptosis.
62
How does venetoclax work?
It is a Bcl-2 inhibitor used to treat CLL and AML.
63
What is a challenge with BH3 mimetics?
They can cause thrombocytopenia due to effects on Bcl-xL in platelets.
64
What combination strategy improves TRAIL-based therapies?
Combining TRAIL with chemotherapy or sensitizers like HDAC inhibitors.
65
How can apoptosis markers be used in diagnostics?
Levels of cleaved caspase-3 or DNA fragmentation (TUNEL assay) indicate apoptosis.
66
What is the TUNEL assay?
A method to detect DNA fragmentation as a marker of apoptosis.
67
Why is apoptosis a desired effect in cancer therapy?
It allows selective killing of cancer cells while sparing normal ones.
68
What is the difference between extrinsic and intrinsic initiator caspases?
Caspase-8 (extrinsic) vs. caspase-9 (intrinsic).
69
What is cross-talk in apoptosis?
When signals from extrinsic apoptosis activate intrinsic pathway via BID cleavage.
70
How can mitochondria regulate both energy and apoptosis?
They produce ATP and release pro-apoptotic factors under stress.
71
What role do reactive oxygen species (ROS) play in apoptosis?
Excess ROS can trigger mitochondrial outer membrane permeabilization.
72
What is the role of the Bcl-2:BAX ratio?
A high ratio inhibits apoptosis, a low ratio promotes it.
73
What happens to the nucleus during apoptosis?
Chromatin condenses, DNA fragments, and nuclear envelope disintegrates.
74
What are apoptotic bodies?
Membrane-bound vesicles containing cellular fragments, which are phagocytosed.
75
How does apoptosis differ morphologically from necrosis?
Apoptosis has cell shrinkage and fragmentation, necrosis has swelling and rupture.
76
What is a proto-oncogene?
A normal gene that promotes cell growth and division, which can become an oncogene when mutated.
77
What is an oncogene?
A mutated or overexpressed gene that promotes uncontrolled cell proliferation.
78
What is a tumor suppressor gene?
A gene that normally inhibits cell division or promotes apoptosis to prevent tumor formation.
79
How do proto-oncogenes become oncogenes?
Through gain-of-function mutations such as point mutations, gene amplification, or chromosomal translocations.
80
How do tumor suppressor genes contribute to cancer?
Loss-of-function mutations in both alleles eliminate control over cell growth.
81
What is loss of heterozygosity (LOH)?
Loss of the normal allele in a heterozygous individual, leading to unopposed mutation effects.
82
What is the role of p53?
A tumor suppressor that halts the cell cycle or induces apoptosis in response to DNA damage.
83
What happens when p53 is mutated?
Cells fail to undergo apoptosis or repair, accumulating mutations and becoming tumorigenic.
84
In which syndrome is p53 germline mutation inherited?
Li-Fraumeni syndrome.
85
What is the function of the Rb protein?
It inhibits cell cycle progression from G1 to S phase by binding E2F transcription factors.
86
What happens when Rb is inactivated?
Cells can continuously enter S phase, promoting uncontrolled proliferation.
87
What is the difference between sporadic and hereditary retinoblastoma?
Sporadic involves two somatic hits; hereditary involves one inherited mutation plus a second somatic hit.
88
What is the function of BRCA1 and BRCA2?
They help repair DNA double-strand breaks via homologous recombination.
89
What cancers are associated with BRCA mutations?
Breast, ovarian, and prostate cancers.
90
Are BRCA mutations dominant or recessive?
They are inherited in a dominant fashion but functionally recessive at the cellular level.
91
What is the oncogenic version of Ras?
A Ras protein with a mutation that prevents GTP hydrolysis, keeping it constitutively active.
92
How does HER2 contribute to cancer?
Gene amplification leads to overexpression and increased growth signaling.
93
What is BCR-ABL?
A fusion oncogene from t(9;22) translocation that encodes a constitutively active tyrosine kinase.
94
How does APC mutation contribute to cancer?
Loss of APC disrupts β-catenin regulation, promoting colorectal cancer.
95
What role does PTEN play?
It inhibits the PI3K/Akt pathway, acting as a tumor suppressor.
96
What happens when TGF-β signaling is lost?
Cells fail to respond to anti-growth signals, contributing to tumorigenesis.
97
What is Knudson's two-hit hypothesis?
Both alleles of a tumor suppressor gene must be inactivated for cancer to develop.
98
What is a dominant negative mutation?
A mutant protein that interferes with the function of the normal protein (e.g., mutant p53).
99
Why are tumor suppressors often recessive at the cellular level?
Because one functional copy is usually sufficient to regulate growth.
100
What type of mutation is often seen in the Ras oncogene?
Point mutations that prevent GTP hydrolysis, keeping Ras active.
101
What cancers commonly involve Ras mutations?
Pancreatic, colorectal, and lung cancers.
102
What is the role of MYC in cancer?
It is a transcription factor that promotes cell growth and is often overexpressed or translocated in cancers.
103
Which chromosomal translocation leads to Burkitt lymphoma?
t(8;14) involving MYC and IgH genes.
104
What role does CDKN2A (p16INK4A) play in cancer?
It inhibits cyclin-dependent kinases to prevent Rb phosphorylation and cell cycle progression.
105
Which tumor suppressor gene is commonly lost in colorectal cancer?
APC gene.
106
What is the significance of the SMAD family?
SMADs transduce signals from TGF-β receptors and act as tumor suppressors.
107
How is HER2 status assessed in breast cancer?
By immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
108
What therapy targets BCR-ABL fusion protein?
Imatinib (Gleevec), a tyrosine kinase inhibitor.
109
How does PARP inhibition work in BRCA-mutated cancers?
It exploits synthetic lethality; BRCA-deficient cells rely on PARP for DNA repair and die when it's blocked.
110
What is a gene amplification?
An increase in the number of copies of a gene, often leading to oncogene overexpression.
111
What is a chromosomal translocation?
A rearrangement where parts of different chromosomes exchange places, potentially forming fusion oncogenes.
112
What is a caretaker gene?
A gene that helps maintain genomic stability, e.g., by repairing DNA damage.
113
How can tumor suppressors be silenced without mutation?
By promoter hypermethylation or histone modification (epigenetic silencing).
114
What is the impact of histone deacetylation on gene expression?
It leads to chromatin condensation and transcriptional repression.
115
What is oncogene addiction?
The dependence of cancer cells on a single overactive oncogene for survival.
116
How can understanding tumor suppressor loss guide therapy?
Loss of checkpoint genes like p53 may increase sensitivity to DNA-damaging agents.
117
What is synthetic lethality?
When the combination of two gene defects leads to cell death, but each defect alone is non-lethal.
118
How do dominant negative p53 mutations contribute to cancer?
They block wild-type p53 function, disabling its tumor suppressor activity.
119
Why is Rb considered a gatekeeper of the cell cycle?
Because it controls the G1/S transition by regulating E2F transcription factors.
120
What is haploinsufficiency?
When one functional copy of a gene is insufficient to maintain normal function, contributing to cancer.
121
What role does ATM play in tumor suppression?
It detects DNA double-strand breaks and activates repair or cell cycle arrest pathways.
122
What is invasion in cancer?
The local movement of cancer cells into surrounding tissues.
123
What is metastasis?
The spread of cancer cells to distant organs via the bloodstream or lymphatic system.
124
Why is metastasis clinically important?
It is the leading cause of cancer-related deaths due to organ failure and treatment resistance.
125
What is epithelial-to-mesenchymal transition (EMT)?
A process where epithelial cells lose polarity and adhesion, gaining migratory and invasive properties.
126
What changes occur during EMT?
Loss of E-cadherin, gain of N-cadherin and vimentin, reorganization of cytoskeleton.
127
Which transcription factors promote EMT?
Snail, Slug, Twist, and ZEB1/2.
128
What is E-cadherin and why is it important?
A cell-cell adhesion molecule; its loss promotes invasion and metastasis.
129
What is integrin switching?
The change in integrin subtypes to favor migration and interaction with new ECM environments.
130
What are matrix metalloproteinases (MMPs)?
Enzymes that degrade extracellular matrix components to facilitate invasion.
131
What regulates MMP activity?
Tissue inhibitors of metalloproteinases (TIMPs).
132
Which cells produce MMPs in the tumor microenvironment?
Cancer cells and stromal cells like fibroblasts and macrophages.
133
What is intravasation?
Entry of cancer cells into the bloodstream or lymphatic system.
134
What is extravasation?
Exit of cancer cells from the vasculature into distant tissue.
135
What is anoikis?
A form of apoptosis triggered when cells detach from the ECM.
136
How do cancer cells resist anoikis?
By upregulating survival signals such as PI3K/Akt or integrin switching.
137
What is the pre-metastatic niche?
A primed environment in distant tissue that supports future metastatic colonization.
138
What is the 'seed and soil' hypothesis?
Cancer cells ('seeds') preferentially grow in specific organs ('soil') based on microenvironmental compatibility.
139
What is organ tropism in metastasis?
The tendency of certain cancers to metastasize to specific organs.
140
Which cancer often metastasizes to bone?
Prostate cancer.
141
Which cancer commonly spreads to the brain?
Lung cancer.
142
What is the role of CXCR4/CXCL12 in metastasis?
Chemokine signaling that directs cancer cell homing to specific tissues.
143
What is the role of CAFs in metastasis?
Cancer-associated fibroblasts secrete factors like MMPs and TGF-β to promote invasion.
144
How do macrophages aid metastasis?
By releasing growth factors, cytokines, and enzymes that support migration and angiogenesis.
145
What imaging techniques detect metastases?
CT, MRI, PET, and bone scans.
146
Why is metastatic cancer hard to treat?
It is heterogeneous, often resistant to therapy, and located in critical organs.
147
What is collective invasion?
Groups of cancer cells migrate together while maintaining cell-cell contacts.
148
What is the role of VEGF in metastasis?
It promotes angiogenesis, allowing tumors to access the bloodstream.
149
What is perineural invasion?
Cancer cells invade along nerve sheaths, often seen in pancreatic and prostate cancers.
150
How does TGF-β contribute to EMT?
It activates transcription factors like Snail and Twist that repress E-cadherin expression.
151
What is the role of β-catenin in invasion?
When released from E-cadherin, it enters the nucleus to promote EMT and migration-related gene expression.
Molecular switch:
In epithelial cells → maintains adhesion via E-cadherin
In EMT + invasion → shifts to a transcriptional regulator, activating mesenchymal and invasive gene programmes
152
How do mesenchymal cells differ from epithelial cells?
Mesenchymal cells are motile, invasive, and resistant to apoptosis, whereas epithelial cells are stationary and adhesive.
153
What are circulating tumor cells (CTCs)?
Cancer cells that have detached from the primary tumor and circulate in the bloodstream.
154
How do CTCs survive shear stress and immune attack?
By forming clusters, associating with platelets, and upregulating survival pathways.
155
What is the epithelial-mesenchymal plasticity?
The ability of tumor cells to reversibly switch between epithelial and mesenchymal states.
156
What is the role of endothelial adhesion molecules in extravasation?
They allow cancer cells to attach to vessel walls before exiting into tissues.
157
How do proteases aid in extravasation?
They break down endothelial junctions and basement membranes.
158
What is dormancy in metastasis?
A state where disseminated tumor cells remain quiescent and undetectable before reactivating.
159
What is micrometastasis?
A small number of cancer cells that have spread to distant tissues but are not clinically detectable.
160
Why are micrometastases clinically significant?
They can remain dormant and later reactivate to form overt metastases.
161
What is the prognosis of metastatic vs. localized cancer?
Metastatic cancer has a significantly worse prognosis.
162
How do inflammatory cytokines promote invasion?
They activate NF-κB and other pathways that promote EMT and survival.
163
How do platelets contribute to metastasis?
They protect circulating tumor cells and facilitate extravasation.
164
What is lymphatic metastasis?
Cancer spread through lymphatic vessels to nearby lymph nodes and beyond.
165
What is vascular mimicry?
The ability of aggressive cancer cells to form vessel-like structures without endothelial cells.
166
How do exosomes influence metastasis?
They carry proteins and RNAs that modulate distant tissues to create pre-metastatic niches.
167
What is autocrine motility factor (AMF)?
A factor secreted by tumor cells to stimulate their own migration and invasion.
168
What is the Warburg effect?
A phenomenon where cancer cells favor glycolysis for energy production even in the presence of oxygen.
169
Why do cancer cells use aerobic glycolysis?
It provides rapid ATP and intermediates for biosynthesis, despite being less efficient than oxidative phosphorylation.
170
What is lactate's role in the tumor microenvironment?
It acidifies the environment, suppresses immune responses, and promotes invasion.
171
What enzyme converts pyruvate to lactate?
Lactate dehydrogenase (LDH).
172
Do cancer cells still use mitochondria?
Yes, for biosynthesis, redox balance, and some ATP production.
173
What is glutaminolysis?
The metabolic conversion of glutamine to feed the TCA cycle and support nucleotide/lipid synthesis.
174
Why is glutamine important in cancer?
It supports energy production, redox homeostasis, and macromolecule synthesis.
175
What is HIF-1α?
Hypoxia-inducible factor 1-alpha, a transcription factor stabilized in low oxygen conditions.
176
What does HIF-1α promote?
Expression of glycolytic enzymes, VEGF, and GLUT1 to support glycolysis and angiogenesis.
177
How does HIF-1α contribute to the Warburg effect?
It induces glycolysis and lactate production genes under normoxic conditions in cancer.
178
What is mTOR?
A kinase that promotes cell growth and metabolism by stimulating protein synthesis and glycolysis.
179
How does AMPK counter cancer metabolism?
It senses low energy and inhibits anabolic processes by opposing mTOR signaling.
180
How does the PI3K/Akt pathway affect metabolism?
It promotes glucose uptake, glycolysis, and lipid biosynthesis.
181
What is GLUT1?
A glucose transporter often overexpressed in cancer cells to support increased glucose uptake.
182
Why do cancer cells upregulate nutrient transporters?
To sustain high rates of glucose, amino acid, and lipid uptake for rapid growth.
183
What is a potential therapeutic target in glycolysis?
LDH-A, which is key to converting pyruvate to lactate.
184
What drug targets glutaminase?
CB-839 (Telaglenastat), which inhibits glutamine metabolism in cancer.
185
How can targeting metabolism enhance immunotherapy?
By reducing lactate production, improving immune cell function in the tumor.
186
How is cancer metabolism visualized clinically?
Through FDG-PET imaging, which detects high glucose uptake.
187
What is FDG in PET scans?
Fluorodeoxyglucose, a radioactive glucose analog taken up by metabolically active cells.
188
Why is FDG-PET effective for cancer detection?
Cancer cells show higher glycolysis and glucose uptake than normal tissues.
189
What is PKM2 and its role in cancer?
Pyruvate kinase M2 isoform is preferentially expressed in cancer cells to regulate glycolysis and support anabolic metabolism.
190
What is hexokinase II and why is it significant in cancer?
An enzyme that phosphorylates glucose, often bound to mitochondria in cancer cells to promote survival.
191
How does lactate help tumors evade immune response?
It inhibits T-cell function and promotes an immunosuppressive microenvironment.
192
Why do cancer cells increase lipid synthesis?
To support membrane production and energy storage for rapid proliferation.
193
Which enzyme is key for fatty acid synthesis in cancer?
Fatty acid synthase (FASN).
194
What is the role of SREBPs in cancer?
Sterol regulatory element-binding proteins activate genes for lipid and cholesterol synthesis.
195
What role does NADPH play in cancer metabolism?
It maintains redox balance and is used in biosynthesis of lipids and nucleotides.
196
How do cancer cells generate NADPH?
Via the pentose phosphate pathway and malic enzyme activity.
197
What is the function of glutathione in cancer cells?
A major antioxidant that helps neutralize ROS and support survival.
198
What is serine biosynthesis used for in cancer?
It supports nucleotide synthesis and redox balance.
199
What is asparagine's role in cancer?
It supports protein synthesis and may act as a nutrient exchange factor.
200
Why is IDH1/2 mutation important in cancer?
It produces 2-hydroxyglutarate, an oncometabolite that alters gene expression.
201
What is 2-hydroxyglutarate (2-HG)?
An oncometabolite produced by mutant IDH that inhibits DNA and histone demethylation.
202
How does metabolism influence epigenetics?
Metabolites like acetyl-CoA and 2-HG affect histone and DNA modifications.
203
What is acetyl-CoA's role in gene regulation?
It provides acetyl groups for histone acetylation, influencing gene expression.
204
How does hypoxia influence cancer metabolism?
It stabilizes HIF-1α and shifts metabolism toward glycolysis and angiogenesis.
205
How does acidity of the tumor environment affect treatment?
It can reduce drug uptake and impair immune function, contributing to resistance.
206
How do stromal cells support tumor metabolism?
They can provide nutrients like lactate and alanine to fuel tumor cells.
207
Why is targeting glutaminase a viable cancer therapy?
Cancer cells are often 'glutamine addicted' and depend on glutaminase for survival.
208
What are the effects of mTOR inhibitors in cancer?
They reduce protein synthesis, glycolysis, and cell growth.
209
How might AMPK activators act as anti-cancer agents?
By mimicking energy stress and shutting down anabolic metabolism.
210
What is metabolic plasticity?
The ability of cancer cells to switch between different metabolic pathways depending on environment.
211
How do metastatic cancer cells adapt metabolically?
They shift to oxidative metabolism or use fatty acids in energy-poor environments.
212
How does cancer metabolism affect immune cell function?
Tumor metabolism can deplete nutrients and produce immunosuppressive metabolites like lactate.
213
What is arginine depletion and how does it affect immunity?
Arginase-expressing cells reduce arginine levels, impairing T-cell activity.
214
What is metabolic symbiosis?
A phenomenon where different tumor regions exchange metabolites to sustain growth.
215
What is the link between oncogenes and metabolism?
Oncogenes like MYC, KRAS, and Akt drive metabolic reprogramming.
216
What is the role of mitochondria in therapy resistance?
They help manage oxidative stress and support survival under drug pressure.
217
How is the Warburg effect regulated at the gene level?
Via transcription factors like MYC and HIF-1α that upregulate glycolytic genes.
218
How does MYC promote aerobic glycolysis?
By inducing glycolytic enzymes and glutamine metabolism genes.
219
What happens to mitochondrial oxidative phosphorylation in Warburg effect?
It is downregulated or uncoupled in favor of glycolysis, despite oxygen being present.
220
What are glutaminase isoforms and their relevance?
GLS1 and GLS2 are enzymes converting glutamine to glutamate; often upregulated in cancer.
221
Why do cancer cells rely on non-essential amino acids?
They support nucleotide biosynthesis and redox balance under nutrient stress.
222
What is alanine shuttling in tumors?
Stromal cells release alanine, which is taken up by cancer cells and used as a carbon source.
223
What is the reverse Warburg effect?
Cancer-associated fibroblasts undergo aerobic glycolysis and feed lactate to cancer cells for oxidative metabolism.
224
What are monocarboxylate transporters (MCTs)?
Proteins that export or import lactate and pyruvate; MCT1 and MCT4 are common in tumors.
225
How does lactate shuttle between stromal and cancer cells?
Via MCTs; lactate from fibroblasts is used oxidatively by tumor cells.
226
How does acetyl-CoA link glucose metabolism to lipid synthesis?
Citrate from the TCA cycle is converted to acetyl-CoA in cytoplasm for fatty acid synthesis.
227
How does cholesterol metabolism affect cancer?
It supports membrane synthesis and signaling domains like lipid rafts.
228
What is the mevalonate pathway's role in cancer?
It produces cholesterol and isoprenoids, essential for cell growth and oncogenic signaling.
229
What is oxidative stress?
A condition of excessive reactive oxygen species (ROS) that can damage DNA, proteins, and lipids.
230
How do cancer cells control ROS levels?
By upregulating antioxidants like glutathione and NADPH-generating enzymes.
231
How does NRF2 support cancer survival?
By activating genes that manage oxidative stress and maintain redox homeostasis.
232
What is ferroptosis?
An iron-dependent form of cell death associated with lipid peroxidation and redox imbalance.
233
How does AMPK sense energy levels?
It is activated by high AMP/ATP ratio and inhibits mTOR to reduce energy expenditure.
234
What are the downstream effects of mTORC1 activation?
Increased protein synthesis, lipid biosynthesis, and glycolysis.
235
How does leucine activate mTOR?
It binds to sensors that stimulate mTORC1 activity.
236
How does 2-hydroxyglutarate (2-HG) promote cancer?
It inhibits dioxygenases that regulate DNA/histone demethylation, causing epigenetic dysregulation.
237
How does α-ketoglutarate (α-KG) maintain normal epigenetic state?
It is a cofactor for demethylases that regulate gene expression.
238
What is the significance of succinate and fumarate in cancer metabolism?
Accumulation due to TCA mutations can inhibit α-KG-dependent enzymes and stabilize HIF-1α.
239
How do TAMs (tumor-associated macrophages) influence metabolism?
They secrete cytokines that promote glycolysis and suppress immunity.
240
How do adipocytes support cancer metabolism?
They provide fatty acids and other metabolites that fuel tumor growth.
241
How does lactate influence angiogenesis?
It stimulates VEGF production through HIF-1α stabilization.
242
Why do T cells struggle in the tumor microenvironment?
They face competition for glucose and are suppressed by lactate and adenosine.
243
How does IDO affect immune responses?
It catabolizes tryptophan, limiting T-cell proliferation and supporting regulatory T cells.
244
What is metabolic synthetic lethality?
Targeting metabolic pathways that are essential only in cancer cells due to oncogenic context.
245
How can dietary restriction impact cancer?
Limiting nutrients like methionine or glucose may starve certain tumor types.
246
What are the challenges of targeting cancer metabolism?
Tumor heterogeneity, metabolic plasticity, and toxicity to normal tissues.
247
What is the role of the immune system in cancer?
To detect and eliminate abnormal cells through immune surveillance.
248
What are the two main arms of the immune system?
Innate immunity and adaptive immunity.
249
What cells are part of innate immunity?
Macrophages, dendritic cells, NK cells, neutrophils.
250
What cells are part of adaptive immunity?
T cells (CD4+, CD8+), B cells, and antibodies.
251
What is immune surveillance?
The process by which the immune system detects and eliminates emerging tumor cells.
252
What is cancer immunoediting?
A process with three phases: elimination, equilibrium, and escape.
253
What happens in the escape phase of immunoediting?
Tumor variants evade immune detection and begin to grow uncontrollably.
254
What are tumor-associated antigens (TAAs)?
Normal proteins that are overexpressed or aberrantly expressed in tumors.
255
What are tumor-specific antigens (TSAs)?
Antigens that arise from mutations and are unique to tumor cells (neoantigens).
256
Why are neoantigens important in immunotherapy?
They are highly immunogenic and recognized as foreign by T cells.
257
What is the role of MHC-I in tumor immunity?
It presents tumor antigens to CD8+ cytotoxic T cells.
258
How do tumors evade MHC-I presentation?
By downregulating MHC-I expression or altering antigen processing machinery.
259
How do tumors evade immune detection?
By suppressing MHC-I, secreting immunosuppressive cytokines, and recruiting regulatory cells.
260
What is PD-L1 and how does it affect immunity?
PD-L1 binds to PD-1 on T cells and inhibits their activity, helping tumors evade immune attack.
261
What are regulatory T cells (Tregs)?
A subset of T cells that suppress immune responses and are often enriched in tumors.
262
What are MDSCs?
Myeloid-derived suppressor cells that inhibit T cell responses in tumors.
263
What is the role of immune checkpoints?
They regulate immune activation and prevent autoimmunity.
264
What are common immune checkpoints targeted in cancer?
CTLA-4 and PD-1/PD-L1.
265
What drugs inhibit PD-1 or PD-L1?
Nivolumab, pembrolizumab (PD-1) and atezolizumab (PD-L1).
266
What drug inhibits CTLA-4?
Ipilimumab.
267
What is CAR-T cell therapy?
A therapy where T cells are engineered to express chimeric antigen receptors that target cancer cells.
268
What cancers are CAR-T cells approved for?
Certain leukemias and lymphomas, especially B cell malignancies targeting CD19.
269
What are cytokine therapies?
Use of interleukins like IL-2 or IFN-α to boost immune responses.
270
What is the tumor immune microenvironment (TIME)?
The mix of immune cells, cytokines, and stromal cells in and around the tumor.
271
What role do tumor-associated macrophages (TAMs) play?
They can be polarized to suppress immune responses and support tumor growth.
272
What occurs in the elimination phase of immunoediting?
Innate and adaptive immune systems recognize and destroy nascent tumor cells.
273
What is the equilibrium phase in immunoediting?
A phase where immune pressure selects for tumor variants that can evade detection.
274
How do NK cells detect tumor cells?
By recognizing cells with low MHC-I expression and activating through stress ligands.
275
What are activating receptors on NK cells?
NKG2D, NKp30, NKp44 — bind ligands expressed on stressed or transformed cells.
276
How do tumors evade NK cell killing?
By shedding NKG2D ligands and expressing HLA-E to engage inhibitory NK receptors.
277
What is the role of dendritic cells (DCs)?
They process and present antigens to T cells, initiating adaptive immune responses.
278
How do tumors impair DC function?
By secreting immunosuppressive cytokines like IL-10 and TGF-β.
279
What are potential adverse effects of checkpoint inhibitors?
Autoimmune-like side effects called immune-related adverse events (irAEs).
280
Why do some tumors not respond to checkpoint inhibitors?
Due to low mutation burden, lack of neoantigens, or immunosuppressive microenvironment.
281
What are biomarkers of checkpoint therapy success?
PD-L1 expression, high TMB, and presence of TILs.
282
What are cancer vaccines?
Vaccines that aim to stimulate immune responses against tumor antigens.
283
What is Provenge (sipuleucel-T)?
An FDA-approved DC-based vaccine for prostate cancer.
284
What are neoantigen vaccines?
Vaccines customized to target tumor-specific mutated peptides.
285
What is the rationale for combining immunotherapy with chemotherapy?
Chemotherapy can increase antigen release and reduce suppressive immune cells.
286
How does radiotherapy aid immunotherapy?
It induces immunogenic cell death and upregulates MHC and danger signals.
287
What is an abscopal effect?
Regression of tumors distant from a radiotherapy site, potentially immune-mediated.
288
What is a 'hot' tumor?
A tumor with abundant T cell infiltration and active immune responses.
289
What is a 'cold' tumor?
A tumor lacking immune infiltration or containing suppressive immune cells.
290
How can cold tumors be converted to hot?
Using therapies like radiotherapy, oncolytic viruses, or TLR agonists.
291
What are bispecific T-cell engagers (BiTEs)?
Antibodies that link T cells to tumor antigens for directed killing.
292
What is adoptive T cell therapy?
Infusion of ex vivo-expanded or engineered tumor-specific T cells.
293
What role does IL-2 play in immunotherapy?
It stimulates T cell and NK cell proliferation, used in melanoma and renal cancer.
294
What is tumor-promoting inflammation?
Chronic inflammation that enhances proliferation, angiogenesis, and immune evasion.
295
How does TGF-β promote tumor immune evasion?
By suppressing effector T cells and promoting Tregs.
296
What is the role of IFN-γ in tumor immunity?
Activates macrophages and enhances antigen presentation, important for tumor clearance.
297
What are tertiary lymphoid structures (TLSs)?
Ectopic lymphoid tissues found in tumors that may support anti-tumor immunity.
298
What are TILs and their significance?
Tumor-infiltrating lymphocytes — high presence is often a positive prognostic marker.
299
What is LAG-3?
An immune checkpoint receptor under investigation as a new immunotherapy target.
300
What is TIM-3?
A checkpoint receptor associated with T cell exhaustion and immune evasion.
301
What is TIGIT?
An inhibitory receptor on T and NK cells; potential target in cancer immunotherapy.
302
What is a hormone?
A signaling molecule secreted into the bloodstream that regulates physiology and behavior.
303
What are steroid hormones?
Lipid-soluble hormones derived from cholesterol, including estrogens, androgens, and glucocorticoids.
304
What is the difference between endocrine and paracrine signaling?
Endocrine signals travel through blood; paracrine signals act locally.
305
What is the estrogen receptor (ER)?
A nuclear receptor activated by estrogen that regulates gene expression.
306
What cancers commonly express ER?
Breast, ovarian, and endometrial cancers.
307
What is the androgen receptor (AR)?
A nuclear receptor activated by androgens like testosterone and dihydrotestosterone (DHT).
308
What cancer type is primarily driven by AR?
Prostate cancer.
309
What are hormone-dependent cancers?
Cancers that rely on hormones for growth, such as ER+ breast cancer and prostate cancer.
310
What are hormone-independent cancers?
Cancers that no longer require hormones to proliferate, often seen in late-stage disease.
311
What causes the shift from hormone dependence to independence?
Mutations in receptors, alternative signaling, or receptor amplification.
312
What is tamoxifen?
A selective estrogen receptor modulator (SERM) that blocks ER in breast tissue.
313
What are aromatase inhibitors?
Drugs that block the conversion of androgens to estrogens in postmenopausal women.
314
Name three aromatase inhibitors.
Anastrozole, letrozole, exemestane.
315
What is fulvestrant?
A selective estrogen receptor degrader (SERD) used in ER+ breast cancer.
316
What is androgen deprivation therapy (ADT)?
Treatment to reduce androgen levels or block androgen receptors in prostate cancer.
317
What are anti-androgens?
Drugs that block androgen receptors, e.g., bicalutamide and enzalutamide.
318
What are LHRH agonists?
Drugs like leuprolide that suppress testosterone production by acting on the pituitary.
319
What is aromatase?
An enzyme that converts androgens to estrogens, targeted in breast cancer therapy.
320
Where is aromatase highly expressed in postmenopausal women?
Adipose tissue.
321
What is 5α-reductase?
An enzyme that converts testosterone to dihydrotestosterone (DHT).
322
How do breast cancers become resistant to tamoxifen?
Through mutations in ER, activation of growth factor pathways, or altered co-regulators.
323
What is ESR1 mutation?
A mutation in the estrogen receptor that makes it constitutively active without estrogen.
324
How do prostate cancers resist ADT?
By AR amplification, AR mutations, or producing their own androgens.
325
What are endocrine-disrupting chemicals (EDCs)?
Environmental chemicals that interfere with hormonal signaling.
326
What is bisphenol A (BPA)?
A synthetic compound that mimics estrogen and may contribute to cancer risk.
327
What does ER+ mean in breast cancer diagnosis?
The tumor expresses estrogen receptor and may respond to anti-estrogen therapy.
328
What is HER2 and how does it interact with hormone signaling?
HER2 is a growth factor receptor; HER2+/ER+ tumors may show cross-talk and resistance.
329
Why are hormone therapies often first-line in ER+ breast cancer?
They are effective and generally have fewer side effects than chemotherapy.
330
Why is hormone therapy less effective in triple-negative breast cancer?
Because these tumors lack ER, PR, and HER2, and don’t respond to hormone blockade.
331
What is genomic hormone signaling?
Activation of nuclear hormone receptors leading to transcriptional regulation.
332
What is non-genomic hormone signaling?
Rapid signaling through membrane-associated receptors activating kinase pathways.
333
Which kinase pathways are activated by non-genomic hormone signaling?
MAPK and PI3K/Akt.
334
What are co-activators and co-repressors?
Proteins that modulate transcriptional activity of hormone receptors.
335
Why are aromatase inhibitors more effective post-menopause?
Estrogen production shifts to peripheral aromatization; ovaries are inactive.
336
Why is tamoxifen preferred in premenopausal women?
It blocks ER while preserving ovarian function, which remains active pre-menopause.
337
What is ovarian suppression therapy?
Use of drugs (e.g. GnRH agonists) or surgery to shut down estrogen production from ovaries.
338
What is the role of progesterone receptor (PR) in cancer?
It is often co-expressed with ER and associated with favorable prognosis.
339
What is the relevance of hormone signaling in endometrial cancer?
Estrogen promotes endometrial proliferation and unopposed estrogen increases risk.
340
How does hormonal therapy help in ovarian cancer?
It may slow growth in ER+ low-grade serous ovarian cancers.
341
How does HER2 interact with ER signaling?
HER2 can activate ER in a ligand-independent manner, contributing to resistance.
342
Why is combining HER2-targeted therapy with hormone therapy beneficial?
It may block both proliferative pathways and overcome resistance.
343
What is enzalutamide?
A next-generation anti-androgen that blocks AR signaling more effectively than older agents.
344
What is abiraterone?
A CYP17 inhibitor that blocks androgen synthesis in prostate cancer.
345
What is triple therapy in prostate cancer?
Combining ADT, AR-targeted therapy, and chemotherapy.
346
How can epigenetics contribute to hormone therapy resistance?
Histone and DNA modifications alter receptor expression and downstream signaling.
347
How does FOXA1 mutation affect ER function?
It alters chromatin accessibility, modifying ER transcriptional activity.
348
What is the Ki-67 index used for in hormone-responsive cancers?
It measures proliferation; higher values may suggest less responsiveness to hormone therapy.
349
What is lobular breast cancer and its hormone relevance?
A subtype typically ER+/PR+ and responsive to hormone therapy.
350
Why monitor bone health in hormone therapy?
Estrogen depletion can reduce bone density, increasing fracture risk.
351
What is chemoprevention?
Using drugs like tamoxifen or raloxifene to reduce breast cancer risk in high-risk individuals.
352
What is the HPG axis?
The hypothalamic-pituitary-gonadal axis regulating sex hormone production.
353
How do LHRH agonists affect the HPG axis?
They initially stimulate then downregulate GnRH receptors, suppressing sex hormones.
354
What are the three main traditional cancer treatment modalities?
Surgery, radiotherapy, and chemotherapy.
355
When is surgery most effective in cancer?
In localized tumors with no metastasis.
356
What is adjuvant therapy?
Treatment given after primary therapy (e.g., surgery) to reduce recurrence risk.
357
What is neoadjuvant therapy?
Treatment given before surgery to shrink the tumor.
358
How does radiotherapy kill cancer cells?
By inducing DNA double-strand breaks, especially during replication.
359
What is fractionation in radiotherapy?
Dividing the total dose into multiple smaller doses to maximize cancer kill and spare normal tissue.
360
What is a radiosensitizer?
A drug that enhances the effect of radiation on tumor cells.
361
Name one example of a radiosensitizer.
5-fluorouracil (5-FU).
362
What are alkylating agents?
Drugs that add alkyl groups to DNA, leading to crosslinking and strand breakage.
363
Give an example of an alkylating agent.
Cyclophosphamide or cisplatin.
364
What are antimetabolites?
Drugs that mimic nucleotides and interfere with DNA/RNA synthesis.
365
Give an example of an antimetabolite.
5-fluorouracil (5-FU) or methotrexate.
366
What are topoisomerase inhibitors?
They prevent DNA unwinding, blocking replication and transcription.
367
Name one topoisomerase inhibitor.
Doxorubicin or irinotecan.
368
What are mitotic inhibitors?
Drugs that disrupt microtubule function, preventing mitosis.
369
Example of a mitotic inhibitor?
Paclitaxel or vincristine.
370
What are common side effects of chemotherapy?
Myelosuppression, nausea, vomiting, hair loss, mucositis.
371
Why does chemotherapy cause side effects?
It targets rapidly dividing cells, including healthy ones like bone marrow and GI lining.
372
What is dose-limiting toxicity?
The side effect severity that prevents further dose escalation.
373
How do targeted therapies differ from chemotherapy?
They specifically inhibit molecules/pathways dysregulated in cancer.
374
What is a tyrosine kinase inhibitor (TKI)?
A small molecule that blocks ATP binding to oncogenic kinases.
375
Name an example of a TKI.
Imatinib (BCR-ABL), gefitinib (EGFR).
376
What are monoclonal antibodies?
Lab-made antibodies that bind specific targets on cancer cells.
377
Give an example of a monoclonal antibody used in cancer.
Trastuzumab (HER2), rituximab (CD20).
378
What is the role of PARP in cells?
It helps repair single-strand DNA breaks.
379
Why are PARP inhibitors effective in BRCA-mutant tumors?
BRCA-deficient cells rely on PARP for repair; inhibition leads to cell death (synthetic lethality).
380
Name a PARP inhibitor.
Olaparib or niraparib.
381
How does tamoxifen work?
It binds and blocks the estrogen receptor (ER).
382
What is the function of aromatase inhibitors?
They prevent estrogen synthesis from androgens.
383
What is the role of CDK4/6 in cancer?
They promote G1/S phase transition via Rb phosphorylation.
384
How do CDK4/6 inhibitors work?
They block cell cycle progression in ER+ breast cancer.
385
Give an example of a CDK4/6 inhibitor.
Palbociclib, ribociclib, or abemaciclib.
386
How do cancers become resistant to TKIs?
Via secondary mutations, pathway reactivation, or bypass signaling.
387
Give an example of resistance mutation in EGFR.
T790M mutation in non-small cell lung cancer.
388
How do tumors resist monoclonal antibodies?
Through antigen loss, mutation, or activation of alternative pathways.
389
Why can chemotherapy resistance develop?
Due to drug efflux pumps (e.g., P-glycoprotein), enhanced DNA repair, or apoptosis evasion.
390
What is a predictive biomarker?
A marker that predicts response to a specific therapy.
391
What is HER2 used as a biomarker for?
Selecting breast/gastric cancers for trastuzumab treatment.
392
What biomarker guides EGFR TKI use in lung cancer?
Presence of EGFR-activating mutations.
393
What biomarker predicts PARP inhibitor response?
BRCA1/2 mutation or homologous recombination deficiency.
394
What is a tumor-agnostic therapy?
A therapy effective across cancer types based on a common biomarker.
395
Give an example of a tumor-agnostic therapy.
Pembrolizumab for MSI-high or dMMR tumors.
396
What is MSI-high?
Microsatellite instability caused by defective mismatch repair, linked to immunotherapy response.
397
What is an antibody-drug conjugate (ADC)?
A monoclonal antibody linked to a cytotoxic drug, delivering targeted chemotherapy.
398
Give an example of an ADC.
Trastuzumab emtansine (T-DM1) or sacituzumab govitecan.
399
Why combine immunotherapy with chemotherapy?
Chemo increases antigen release and reduces immunosuppressive cells.
400
Why combine targeted therapy with hormone therapy?
To overcome resistance through pathway cross-talk.
401
What is precision oncology?
Using genetic/molecular information to guide personalized treatment decisions.
402
What is NGS and how is it used in cancer therapy?
Next-generation sequencing identifies mutations, fusions, and biomarkers.
403
Name a clinical program for genomic-guided therapy.
NCI-MATCH or MSK-IMPACT.
404
What is stereotactic body radiotherapy (SBRT)?
Highly focused radiation to treat small tumors with minimal damage to normal tissue.
405
What is brachytherapy?
Internal radiotherapy using implanted radioactive sources.
406
Why are combination regimens used in chemotherapy?
To increase efficacy, reduce resistance, and exploit synergy.
407
What is the CHOP regimen used for?
Treatment of non-Hodgkin lymphoma.
408
What is the goal of metronomic chemotherapy?
Low-dose, continuous chemo to minimize toxicity and target tumor vasculature.
409
What is the mechanism of PD-1 inhibitors?
They block inhibitory PD-1/PD-L1 signaling, restoring T cell activity.
410
What is CTLA-4's role in cancer?
It inhibits early T cell activation; blockade enhances immune priming.
411
What is tumor lysis syndrome?
A life-threatening complication due to rapid tumor cell death and metabolite release.
412
What is febrile neutropenia?
Fever with low neutrophil count, a serious chemotherapy complication.
413
What supportive drugs are used with chemotherapy?
Antiemetics, G-CSF for neutropenia, erythropoietin for anemia.
414
What is the difference between curative and palliative treatment?
Curative aims to eliminate cancer; palliative focuses on symptom relief.
415
What is primary resistance?
When a cancer does not respond to a therapy from the outset.
416
What is acquired resistance?
When a cancer initially responds but later becomes resistant to treatment.
417
What is intrinsic resistance?
Resistance due to inherent properties of the tumor cells.
418
What is extrinsic resistance?
Resistance mediated by external factors like the microenvironment.
419
How can mutation lead to drug resistance?
By altering the drug target, reducing drug binding or effectiveness.
420
What is bypass signaling?
Activation of alternative pathways that compensate for the inhibited one.
421
What are drug efflux pumps?
Proteins like P-glycoprotein that export drugs out of cancer cells.
422
How does epithelial-mesenchymal transition (EMT) promote resistance?
By increasing cell survival and drug efflux capabilities.
423
How can the tumor microenvironment mediate resistance?
By providing survival signals and creating immunosuppressive conditions.
424
What is a prognostic biomarker?
A marker indicating likely patient outcome regardless of treatment.
425
What is a predictive biomarker?
A marker that predicts response to a specific therapy.
426
What is HER2 a predictive biomarker for?
Response to trastuzumab in breast and gastric cancer.
427
What is BRCA mutation predictive of?
Response to PARP inhibitors in breast, ovarian, and prostate cancers.
428
What is PD-L1 expression used for?
Predicting response to immune checkpoint inhibitors.
429
What is MSI-high/dMMR used to predict?
Response to immunotherapy across multiple cancer types.
430
What is next-generation sequencing (NGS)?
A method to rapidly sequence DNA and identify mutations, fusions, and CNVs.
431
What are companion diagnostics?
Tests used to determine if a patient will benefit from a specific drug.
432
What is a liquid biopsy?
A non-invasive test to detect tumor material in blood, such as ctDNA or CTCs.
433
What is ctDNA?
Circulating tumor DNA, fragments of DNA shed by cancer cells into the blood.
434
What are CTCs?
Circulating tumor cells, whole cancer cells found in the bloodstream.
435
What are exosomes?
Small vesicles secreted by cells containing DNA, RNA, and proteins.
436
What is personalized (precision) oncology?
Tailoring cancer therapy based on the genetic/molecular profile of the tumor.
437
What is a molecular tumor board?
A multidisciplinary team reviewing genetic data to guide treatment decisions.
438
What is pharmacogenomics?
The study of how genetic variation affects drug response.
439
What mutation causes resistance to imatinib in CML?
T315I mutation in the BCR-ABL kinase domain.
440
What EGFR mutation causes resistance to first-gen TKIs?
T790M mutation.
441
How do ALK+ lung cancers develop resistance?
Through ALK mutations or activation of bypass pathways like EGFR or MET.
442
What is a static biomarker?
A fixed characteristic present before treatment (e.g., BRCA mutation).
443
What is a dynamic biomarker?
A marker that changes over time or in response to therapy (e.g., ctDNA levels).
444
Why are dynamic biomarkers useful?
They can track treatment response and detect early resistance.
445
What is multi-omics profiling?
Integration of genomics, transcriptomics, proteomics, and metabolomics for cancer analysis.
446
How can proteomics aid cancer therapy?
By revealing active signaling pathways and post-translational modifications.
447
What is transcriptomics?
Study of RNA expression patterns to understand tumor behavior.
448
Why is data integration important in personalized oncology?
Single-omics may miss key mechanisms; integration offers a fuller picture.
449
How is AI used in personalized oncology?
To analyze complex data, predict therapy response, and identify novel biomarkers.
450
What is machine learning?
An AI method that uses data to make predictions or classify outcomes.
451
What are some AI applications in cancer?
Pathology image analysis, genomics interpretation, clinical trial matching.
452
What is analytical validity?
Accuracy and reliability of a biomarker test.
453
What is clinical validity?
Association of the biomarker with disease presence or outcome.
454
What is clinical utility?
Evidence that the biomarker improves clinical decision-making or outcomes.
455
What are basket trials?
Clinical trials that test a drug across multiple cancer types with the same mutation.
456
What are umbrella trials?
Trials testing multiple therapies in a single cancer type based on molecular subtypes.
457
What is adaptive therapy?
Modulating drug dosing to maintain sensitive tumor cell populations and delay resistance.
458
What is the role of real-world evidence?
Using data from clinical practice to support or refine treatment approaches.
459
What is tumor heterogeneity?
Variation in genetic and molecular features within a tumor or between patients.
460
Why is tumor heterogeneity a challenge?
It leads to variable treatment response and resistance development.
461
What is clonal evolution in cancer?
Selection of tumor subclones under therapy pressure, leading to resistance.
462
Why is serial monitoring of ctDNA useful?
It helps detect relapse, resistance, and minimal residual disease early.
463
What is the definition of cancer?
Cancer is a group of diseases in which cells divide and grow uncontrollably, potentially invading other parts of the body.
464
What is a benign tumor?
A non-cancerous tumor that does not spread to other parts of the body.
465
What is metastasis?
The movement of cancer cells from their site of origin to a new location in the body.
466
What is a carcinogen?
A substance or exposure that increases the risk of cancer developing.
467
What is apoptosis?
Programmed cell death that eliminates faulty or damaged cells.
468
What is angiogenesis?
The formation of new blood vessels, a process exploited by tumors for nutrient supply.
469
What is a somatic mutation?
A mutation occurring after conception that is not inherited but passed on to daughter cells.
470
What is a germline mutation?
A mutation present in sperm or egg cells that is inherited by offspring.
471
What is a biopsy?
A sample of tissue taken to examine for disease presence or progression.
472
What are the six classic hallmarks of cancer?
1) Self-sufficiency in growth signals, 2) Insensitivity to anti-growth signals, 3) Evasion of apoptosis, 4) Limitless replicative potential, 5) Sustained angiogenesis, 6) Tissue invasion and metastasis.
473
What does 'self-sufficiency in growth signals' mean in cancer?
Cancer cells can produce their own growth signals or activate pathways independently of external stimuli.
474
How do cancer cells show insensitivity to anti-growth signals?
They often have mutations in tumor suppressor genes like Rb, making them unresponsive to signals that stop cell division.
475
Why is evading apoptosis important for cancer cells?
It allows damaged or abnormal cells to survive and proliferate instead of undergoing programmed cell death.
476
How do cancer cells achieve limitless replicative potential?
By activating telomerase to maintain telomere length and avoid senescence.
477
What is the significance of angiogenesis in tumor growth?
It ensures a steady supply of oxygen and nutrients by forming new blood vessels.
478
What allows cancer cells to invade tissues and metastasize?
Loss of cell adhesion molecules like E-cadherin and secretion of matrix-degrading enzymes enable invasion and metastasis.
479
What are some common risk factors for cancer?
Smoking, alcohol consumption, obesity, infections, genetic predispositions, and environmental exposures.
480
How many mutations typically lead to transformation into a cancer cell?
Usually between 3 to 7 genetic 'hits' or events are required for transformation.
481
What percentage of UK cancer cases are due to tobacco use?
Approximately 15–20%.
482
What percentage of cancer deaths in the UK is cancer responsible for?
Around 25–30%.
