Cancer Flashcards
(148 cards)
1
Q
What are the two heritable properties that define cancer cells?
A
- They reproduce in defiance of normal restraints on cell growth and division. 2. They invade and colonize territories normally reserved for other cells.
2
Q
What is the difference between a benign tumor and a malignant tumor?
A
A benign tumor does not invade surrounding tissue, while a malignant tumor has acquired the ability to invade.
3
Q
What is metastasis in the context of cancer?
A
It is the process by which cancer cells break loose, enter blood or lymphatic vessels, and form secondary tumors at other sites in the body.
4
Q
What is the primary origin of most cancers?
A
A single primary tumor arising from a specific organ.
5
Q
What is the term for the genetic changes that occur in tumor cells?
A
Somatic mutations.
6
Q
What is carcinogenesis linked to?
A
Mutagenesis, which is the production of a change in the DNA sequence.
7
Q
What are the two classes of external agents that provoke genetic changes leading to cancer?
A
- Chemical carcinogens. 2. Radiation (such as x-rays and ultraviolet light).
8
Q
What are epigenetic changes in the context of cancer?
A
Persistent, heritable changes in gene expression resulting from modifications of chromatin structure without alteration of the DNA sequence.
9
Q
What is a neoplasm?
A
A new growth, which can be benign or malignant.
10
Q
What is carcinogenesis?
A
The generation of cancer.
11
Q
What is mutagenesis?
A
The production of a change in the DNA sequence.
12
Q
What genetic defect heightens the risk of cancer in individuals?
A
Defects in DNA repair mechanisms.
13
Q
Why do mutations occur spontaneously even in the absence of mutagens?
A
Due to fundamental limitations on the accuracy of DNA replication and repair.
14
Q
What does the gradual accumulation of mutations in a lineage of cells lead to?
A
The development of cancer.
15
Q
What is tumor progression?
A
The evolution of an initial mild disorder of cell behavior into full-blown cancer.
16
Q
What role does the size of a tumor play in cancer progression?
A
Larger tumor size increases the chance that a cell will undergo a mutation favoring its survival.
17
Q
What does the ‘Big Bang’ theory of cancer evolution propose?
A
Cancer evolution can include sudden genome disruptions that promote rapid phenotypic changes.
18
Q
What characterizes genetically unstable cancer cells?
A
They accumulate genetic changes at an abnormally rapid rate.
19
Q
What can lead to chromosomal abnormalities in cancer cells?
A
Defects in chromosome duplication or segregation during mitosis.
20
Q
What factors complicate cancer therapies?
A
The large amount of genetic diversity in tumors.
21
Q
What does the presence of competing subclones in a tumor indicate?
A
Genetic diversity and complexity within the tumor.
22
Q
What is the initial step in metastasis for cancer cells?
A
Invasion through the basal lamina.
23
Q
What is aneuploidy?
A
A condition where cells have an abnormal number of chromosomes, typically n + 1 or n - 1 karyotypes.
24
Q
What occurs during chromosome mis-segregation?
A
It can lead to aneuploidy or chromothripsis, where chromosomes fail to segregate properly during mitosis.
25
Define micronucleus.
A small nucleus that forms when a lagging chromosome is separated from the main set of chromosomes during cell division.
26
What is chromothripsis?
A phenomenon where a chromosome undergoes fragmentation and reassembly, often seen in lagging chromosomes.
27
How does genome instability contribute to cancer?
It leads to heterogeneity in cancer cells, allowing for diverse phenotypes and clonal evolution.
28
What tissues are common breeding grounds for human cancers?
Self-renewing tissues such as the epidermis, epithelial lining of digestive and reproductive tracts, and bone marrow.
29
What is the relationship between stem cell divisions and cancer risk?
There is a strong correlation; higher frequencies of stem cell divisions in a tissue are associated with increased cancer risk.
30
What role do stem cells play in tissue renewal?
They divide to produce differentiated cells that eventually stop dividing, maintaining tissue homeostasis.
31
What happens when mutations affect normal stem cell differentiation?
They can lead to overproliferation of transit amplifying cells or inhibit their differentiation and death.
32
What are the common hallmarks of cancerous growth?
Altered homeostasis, bypass of proliferation limits, evasion of cell death, altered metabolism, manipulation of tissue environment, and metastasis.
33
What is replicative cell senescence?
A built-in limit to the number of times normal cells can divide, typically due to telomere shortening.
34
How do cancer cells behave differently in their natural environment?
They may survive and proliferate even after being detached from their matrix, unlike normal cells.
35
What is contact inhibition?
The phenomenon where normal cells stop dividing when they touch each other.
36
What is the impact of environmental factors on cancer risk?
Environmental factors can amplify the risk of many cancers, such as the difference in lung cancer incidence between smokers and nonsmokers.
37
What can mutations during cancer progression change in tumor cells?
They can change the direction of cell extrusion, allowing tumor cells to invade surrounding tissues.
38
How do cancer cells differ in terms of contact inhibition?
Cancer cells disregard contact inhibition and continue to grow, piling on top of one another.
39
What happens to normal cells when they become crowded in a tissue?
They are extruded into the lumen and generally undergo apoptosis due to loss of survival signals.
40
What is the mechanism by which cancer cells avoid replicative cell senescence?
They either reactivate the telomerase gene or use a DNA repair process called ALT.
41
What signals do unprotected chromosome ends trigger in normal cells?
They trigger a permanent cell-cycle arrest or cell death.
42
What is necrosis?
A form of cell death that occurs when cells burst open due to lack of oxygen and nutrients.
43
What is the primary metabolic difference between normal differentiated cells and tumor cells?
Tumor cells prioritize glycolysis over oxidative phosphorylation for ATP production.
44
What role does the tumor stroma play in cancer development?
It provides a supportive framework and participates in two-way communication with cancer cells.
45
How do tumors manipulate the immune system?
They invoke inflammatory reactions and establish an immunosuppressive microenvironment.
46
What is metastasis?
The process by which cancer cells spread and multiply at new sites in the body.
47
What is a key characteristic of malignant tumors?
Invasiveness, characterized by disorganized growth and extensions into surrounding tissues.
48
What must cancer cells do to establish colonies in distant organs?
They must penetrate blood or lymphatic vessels and successfully exit into new tissue.
49
What are circulating tumor cells (CTCs)?
Cancer cells that have entered the bloodstream and are used to monitor metastasis.
50
What advantage do clusters of circulating tumor cells have over single cells?
They have a higher rate of giving rise to metastases.
51
What happens to many cancer cells after they enter foreign tissue?
Some die immediately, while others may survive but struggle to proliferate.
52
What happens to tumor cells that enter lymphatic vessels?
They often become trapped in lymph nodes, resulting in lymph-node metastases.
53
What defines cancer cells?
They grow and proliferate in defiance of normal controls and invade surrounding tissues.
54
What is the origin of cancers?
Cancers are thought to originate from a single cell that has experienced an initial mutation.
55
What process reflects tumor progression?
A Darwinian-like process of evolution involving mutation, natural selection, and genomic chaos.
56
What properties do cancer cells acquire as they evolve?
They gain the ability to grow and divide despite normal cell proliferation controls.
57
What are stromal cells?
Other cells present in the tumor microenvironment that the cancer attracts and manipulates.
58
Why are most cancer cells genetically and/or epigenetically unstable?
This instability accelerates the accumulation of further genetic and epigenetic changes required for tumor progression.
59
What mechanisms do cancer cells often have defects in?
Controls that stop cell division or induce apoptosis in response to stress or DNA damage.
60
What are cancer-critical genes?
Genes whose alteration can contribute to the causation or evolution of cancer.
61
What are the two broad classes of cancer-critical genes?
* Proto-oncogenes
* Tumor suppressor genes
62
What is a proto-oncogene?
A gene where a gain-of-function mutation can drive a cell toward cancer.
63
What is an oncogene?
The mutant, overactive or overexpressed form of a proto-oncogene.
64
What is a tumor suppressor gene?
A gene where a loss-of-function mutation can contribute to cancer.
65
How do mutations in oncogenes and tumor suppressor genes promote cancer?
They can cause cells to proliferate when they should not or lead to genetic instability.
66
What are genome maintenance genes?
A subclass of cancer-critical genes whose alteration results in genomic instability.
67
How do oncogenes and tumor suppressor genes differ in their effects?
Oncogenes act in a dominant manner and tumor suppressor genes generally act in a recessive manner.
68
What method was used to identify human oncogenes?
DNA extracted from human tumor cells was introduced into cultured mouse cells to identify abnormally proliferating colonies.
69
What is the role of Ras proteins in cancer?
Normal Ras proteins help transmit signals for cell growth; mutations in Ras genes lead to hyperactive forms that promote cancer.
70
What types of mutations can convert a proto-oncogene into an oncogene?
* Point mutations
* Gene amplification
* Chromosomal rearrangements
71
What is retinoblastoma?
A childhood cancer where tumors develop from neural precursor cells in the immature retina.
72
What are the two forms of retinoblastoma?
* Hereditary
* Nonhereditary
73
What characterizes the hereditary form of retinoblastoma?
Multiple tumors usually arise independently, affecting both eyes.
74
What characterizes the nonhereditary form of retinoblastoma?
Only one eye is affected, and by only one tumor.
75
What is the Rb gene?
A gene that, when mutated or deleted, predisposes individuals to retinoblastoma.
76
What happens to the Rb gene in individuals with the hereditary form of retinoblastoma?
They have a deletion or loss-of-function mutation in one copy of the Rb gene in every somatic cell.
77
What is required for nonhereditary retinoblastoma to occur?
Two independent events that inactivate the same gene on two chromosomes in a single retinal cell lineage.
78
In which types of cancer is the Rb gene often missing?
* Carcinomas of lung
* Carcinomas of breast
* Carcinomas of bladder
79
What is the role of the Rb protein?
It acts as a universal regulator of the cell cycle.
80
What mechanisms can inactivate tumor suppressor genes?
* Chromosomal deletion
* Point mutation
* Epigenetic changes
81
How can epigenetic changes permanently inactivate a tumor suppressor gene?
Through methylation of C nucleotides in CG sequences in its promoter.
82
What is aneuploidy?
A change in chromosome karyotype from the normal number (46).
83
What types of genetic changes can be detected in cancer cell genomes?
* Point mutations
* Copy number variations
* Epigenetic changes
84
What is the relationship between DNA repair genes and certain cancers?
Aberrations in DNA repair genes like Brca1 and Brca2 correlate with high mutation frequencies.
85
What is the impact of methylation on tumor suppressor genes?
Increased methylation can permanently silence tumor suppressor genes.
86
How do histone marks affect gene expression?
Histone marks modulate gene expression by altering chromatin conformation and accessibility to regulatory factors.
## Footnote
This includes transcription factors and chromatin remodeling complexes.
87
What role do epigenetic changes play in cancer development?
Epigenetic changes can modulate gene expression and contribute to tumorigenesis, often cooperating with genetic changes.
## Footnote
They can precede oncogenic mutations or be a result of genetic mutations.
88
What is the effect of the mutant IDH gene in cancers?
Mutant IDH produces elevated levels of 2-hydroxyglutarate, inhibiting enzymes that demethylate DNA, leading to hypermethylation.
## Footnote
This hypermethylation can provide a selective advantage for cancer cell growth.
89
What are cancer-critical genes?
Cancer-critical genes are genes strongly suspected to be causal factors in cancer, estimated to number around 300.
## Footnote
They account for about 1% of the human genome and involve diverse mechanisms.
90
List three pathways commonly disrupted in cancers.
* Rb pathway
* RTK/Ras/PI 3-kinase pathway
* p53 pathway
91
What is the Warburg effect?
The Warburg effect refers to the excessive rate of glycolysis observed in tumor cells.
## Footnote
This effect is associated with abnormal activation of the PI 3-kinase/Akt/mTOR pathway.
92
What is the role of the PI 3-kinase/Akt/mTOR pathway in cancer?
It is critical for cell growth control and is often activated by mutations, allowing cancer cells to grow without normal signals.
## Footnote
Activation leads to increased protein synthesis and glucose uptake.
93
How is the p53 gene related to cancer?
The p53 gene is mutated in about 50% of all cancer cases, highlighting its critical role in regulating responses to stress and DNA damage.
94
What happens when the p53 pathway is disrupted?
Cancer cells can survive and proliferate despite stress and DNA damage due to the loss of normal p53 function.
## Footnote
This pathway is crucial for maintaining cellular integrity in response to pathological conditions.
95
What is the function of p53 protein in cells?
p53 acts as a cellular stress sensor, triggering actions like cell cycle arrest or apoptosis in response to pathological conditions.
## Footnote
p53 concentration rises in response to DNA damage, telomere shortening, hypoxia, osmotic stress, and oxidative stress.
96
What are the two forms of cell death described?
* Apoptosis: a programmed cell death that minimizes damage to the organism
* Necrosis: a chaotic cell death causing inflammation due to spilled contents
## Footnote
Apoptosis involves phagocytosis by neighboring cells, while necrosis leads to disintegration.
97
What does the p53 pathway do in cancer cells?
It is generally inactivated, allowing cancer cells to survive and proliferate despite having damaged genomes.
## Footnote
If p53 is functional, cells with DNA damage will not proliferate.
98
How does p53 inhibit the cell cycle?
By inducing the transcription of p21, which inhibits cyclin-dependent kinase (Cdk) complexes required for progression through the cell cycle.
## Footnote
p21 prevents progression through S phase and DNA replication.
99
How do cancers evolve over time?
Cancers constantly mutate, compete, and diversify, particularly as they metastasize and encounter new selection pressures.
## Footnote
The longer the evolutionary process continues, the harder it becomes to eradicate all cancer cells.
100
What are the stages of colorectal cancer development?
Colorectal cancers progress from benign to malignant tumors through a series of independent genetic and epigenetic changes.
## Footnote
These changes include mutations in genes that regulate cell growth and differentiation.
101
What is the role of stem cells in the renewal of the intestinal epithelium?
Stem cells in intestinal crypts are responsible for the rapid renewal of the epithelial lining in the colon and rectum.
## Footnote
The epithelium is renewed approximately every week.
102
What happens to p53 levels in response to various cellular stresses?
p53 levels increase in response to hyperproliferative signals, DNA damage, hypoxia, and other stresses.
## Footnote
This increase can lead to cell-cycle arrest, senescence, or apoptosis.
103
What is the function of the APC protein?
It inhibits the Wnt signaling pathway by degrading β-catenin.
104
What is hereditary nonpolyposis colorectal cancer (HNPCC)?
A hereditary condition increasing the risk of colon cancer without an increase in polyps.
105
What causes the genetic instability in HNPCC?
Defects in DNA mismatch repair genes.
106
What is the significance of the K-Ras gene in colorectal cancer?
Activating mutations occur later in tumor progression.
107
What is the relationship between p53 loss and oncogene activation?
Loss of p53 allows cancer cells with hyperactive oncogenes to survive.
108
What is the role of the p53 protein in cancer cells with hyperactive oncogenes?
Leads to cell-cycle arrest or death
## Footnote
The p53 protein is crucial in preventing the survival of genetically damaged cells.
109
What must happen for cancer cells with hyperactive oncogenes to survive and progress?
Loss of p53 function
110
What could potentially initiate metastasis according to current understanding?
Epigenetic changes that alter patterns of gene expression
111
What is the epithelial-to-mesenchymal transition (EMT)?
A process that allows epithelial cells to lose polarity and adhesiveness, taking on a mesenchymal phenotype
112
What does EMT enhance in cancer cells?
Migratory behavior
113
What do cancer cells utilize to promote tumorigenesis?
Existing mechanisms and pathways at inappropriate times and places
114
What is the role of genome maintenance genes?
Help maintain genome integrity
115
What is the consequence of inactivating the p53 pathway?
Genetically damaged cells escape apoptosis and continue to proliferate
116
What does the inactivation of the Rb pathway illustrate?
Fundamental importance for cancer protection
117
What types of disturbances must be acquired for cancer development?
* Disturbances in the cell cycle
* Disturbances in cell proliferation
* Disturbances in cell survival pathways
118
What do tumors typically contain in terms of cellular composition?
A heterogeneous mixture of cells, including cancer stem cells
119
What is often correlated with the steps of tumor progression?
Mutations that activate specific oncogenes and inactivate specific tumor suppressor genes
120
What reflects the random way in which inherited changes arise in cancer?
Different combinations of mutations and epigenetic changes found in different types of cancer
121
What are the three levels at which we can attack cancer?
Prevention, diagnosis, and treatment.
122
What are some important classes of environmental cancer risk factors?
* Chemicals in the environment
* Hormones circulating in the body
* Irritations, infections, and tissue damage.
123
What must many chemical carcinogens undergo to become damaging?
Metabolic conversion to a more reactive molecule.
124
What is the most important carcinogen in the world today?
Tobacco smoke.
125
How do DNA tumor viruses cause cancer?
By interfering with controls of the cell cycle and apoptosis.
126
What is the role of PARP in DNA repair?
PARP is involved in repairing single-strand breaks in DNA
## Footnote
Inhibiting PARP can selectively kill cancer cells that are deficient in other DNA repair mechanisms.
127
What happens when both copies of Brca1 or Brca2 are inactivated?
Increased genetic instability and tumor progression
## Footnote
These genes are crucial for repairing DNA double-strand breaks, and their inactivation leads to a higher risk of cancer.
128
What is a significant challenge in cancer treatment?
Eradicating all cancer cells without harming normal cells
## Footnote
Cancer treatments often have harsh side effects due to the similarity between cancerous and normal cells.
129
What is the role of PARP in Brca-deficient cells?
PARP activity kills Brca-deficient cells with extraordinary selectivity while having little effect on normal cells.
## Footnote
PARP is involved in DNA repair, and its inhibition exploits the genetic instability of tumor cells.
130
How do normal cells repair DNA breaks compared to Brca-deficient tumor cells?
Normal cells have two repair pathways (pathway 1 and pathway 2), while Brca-deficient tumor cells have lost pathway 2.
## Footnote
Pathway 1 requires the PARP protein, and pathway 2 relies on Brca1 and Brca2 for homologous recombination.
131
What is the effect of PARP inhibitors on tumors in Brca-deficient patients?
PARP inhibitors cause tumors to regress and delay disease progression with relatively few side effects.
## Footnote
They are also applicable to other cancers with defects in homologous recombination.
132
What is oncogene dependence?
Oncogene dependence refers to cancer cells becoming reliant on the hyperactivity of an initial oncogene due to further mutations or adaptations.
## Footnote
This phenomenon allows targeted therapies to kill cancer cells without significantly harming normal cells.
133
What is the significance of small-molecule inhibitors in cancer treatment?
Small-molecule inhibitors targeting oncogenic proteins, like imatinib for Bcr-Abl, can provide rational methods to treat cancers based on genetic lesions.
## Footnote
Many other inhibitors are being developed for various oncogenic pathways.
134
What is the role of monoclonal antibodies in cancer therapy?
Monoclonal antibodies can target cancer cells, inhibit their growth, or deliver toxins specifically to them.
## Footnote
An example is trastuzumab (Herceptin), which targets Her2 in breast cancer.
135
What are T cells and their function in cancer immunotherapy?
T cells can kill host cells displaying foreign antigens, and harnessing them to attack cancer cells is a key strategy in immunotherapy.
## Footnote
This requires identifying tumor-specific antigens for effective targeting.
136
How does CAR T cell therapy work?
CAR T cell therapy involves collecting a patient's T cells, expanding them, and genetically engineering them to recognize specific tumor antigens.
## Footnote
This therapy has shown high effectiveness against certain blood cancers.
137
What are the potential outcomes of using PARP inhibitors in cancer therapy?
Tumor regression, delay in disease progression, and applicability to other cancers with homologous recombination defects.
## Footnote
These outcomes raise hopes for broader cancer treatment strategies.
138
How do cancer cells manipulate their microenvironment to evade immune responses?
By creating a stroma that promotes tumor growth and suppresses immune responses.
139
What is the role of immune checkpoint mechanisms in the context of cancer?
They prevent excessive immune responses but can also prevent T cells from killing cancer cells.
140
What are immune checkpoint inhibitors designed to do?
Prevent tumor cells from engaging with inhibitory receptors on T cells.
141
Name two specific immune checkpoint receptors involved in cancer therapy.
* PD1 (programmed cell death 1)
* PDL1 (programmed death ligand 1).
142
What phenomenon allows cancer cells to evolve resistance to therapeutic drugs?
Genetic instability.
143
What is multidrug resistance in cancer cells often associated with?
Amplification of the Mdr1 or Abcb1 gene.
144
What type of drug is a PARP inhibitor?
A drug that targets genetic instability.
145
What is the significance of combination therapies in cancer treatment?
They can better target cancer cells and reduce resistance development.
146
What is the purpose of tailoring drug combinations to individual patients?
To address the unique genetic makeup of each patient's cancer.
147
What is the advantage of using organoids in cancer treatment development?
They facilitate patient-specific drug testing.
148
How can anticancer therapies be designed to preferentially destroy cancer cells?
By exploiting properties that distinguish cancer cells from normal cells.
