Intro to Neoplasia, Pathology and Chemotherapy Flashcards
(76 cards)
1
Q
What is the median age of Cancer diagnosis?
A
67
2
Q
Neoplasm
A
new growth, may be benign or malignant
3
Q
Tumor
A
nonspecific term meaning lump or swelling
4
Q
Cancer
A
any MALIGNANT neoplasm
5
Q
Hyperplasia
A
an increase in organ or tissue size due to an increase in the number of cells
6
Q
Metaplasia
A
an adaptive, substitution of one type of adult tissue to another type of adult tissue
7
Q
Dysplasia
A
an abnormal cellular proliferation is which there is a loss of normal architecture
8
Q
Anaplasia
A
a loss of structural differentiation. Cells differentiate
9
Q
Carcinoma
A
malignant neoplasm of squamous epithelial cell origin
10
Q
Adenocarcinoma
A
adeno=gland
malignant neoplasm derived from glandular tissue
11
Q
Sarcoma
A
malignant neoplasm with origin in mesenchymal tissues or its derivatives
example: bone, muscle, fat
12
Q
Lymphoma and Leukemia
A
malignant neoplasms of hematopoietic tissues
13
Q
Melanoma
A
type of cancer of pigment producing cells in the skin or the eye
14
Q
Blastoma
A
malignancies in precursor cells, often called blasts, which are more common in children
15
Q
Teratoma
A
a germ cell neoplasm made of several different differentiated cell/tissue types
16
Q
Myeloid leukemias
A
common myeloid progenitor
17
Q
Lymphocytic leukemias
A
common lymphoid progenitor
18
Q
Lymphomas
A
small lymphocyte–>T lymphocyte and B lymphocyte–> plasma cell
19
Q
Stage 0
A
In situ carcinoma, no sign of local invasion
20
Q
Stage 1
A
microscopic invasion of surrounding tissue
21
Q
Stage 2
A
4-9 Surrounding Lymph nodes are involved
22
Q
Stage 3
A
10 or more surrounding lymph nodes are involved
23
Q
Stage 4
A
Distant metastases are detected
24
Q
What is the numerical staging system based on?
A
largely based on tumor size, location, and number
25
Primary tumor
T
26
TX
Primary tumor cannot be evaluated
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T0
No evidence of primary tumor
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Tis
Carcinoma In Situ: Abnormal cells are present but have not spread to neighboring tissue; although not cancer, CIS may become cancer and is sometimes called preinvasive cancer
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T1, T2, T3, T4
Size and/or extent of invasion of the primary tumor
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Regional Lymph Nodes
N
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NX
Regional lymph nodes cannot be evaluated
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N0
No regional lymph node involvement
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N1, N2, N3
Degree of regional lymph node involvement
34
Distant Metastasis
M
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MX
Distant metastasis cannot be evaluated
36
M0
No distant metastasis
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M1
Distant metastasis is present
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In situ
abnormal cells are present only in the layer of the cells in which they developed
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Localized
cancer is limited to the organ in which it began, without evidence of spread
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Regional
cancer has spread beyond the primary site to nearby lymph nodes or tissues and organs
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Distant
cancer has spread from the primary site to distant tissues or organs or to distant lymph nodes
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G1
Well differentiated (low grade)
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G4
Undifferentiated (high grade)
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Cancer is a disease of progression
Cell with mutation-->Hyperplasia-->Dysplasia-->In situ cancer--> Invasive cancer
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Hallmarks of cancer
1. Sustaining proliferative signaling
2. Avoiding immune destruction
3. Enabling replicative immortality
4. Activating invasion and metastasis
5. Inducing or accessing vasculature
6. Genome instability and mutation
7. Resisting cell death
46
For many tumors the growth of the primary tumor is not going to be life threatening
Cells from a primary tumor can sit in an organ for very long periods of time before metastasizing
Metastasized cells are considered a tumor from the PRIMARY SITE
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v-Src
ONCOGENE: gene that can cause cancer
RSV encodes a protein (v-Src) that is similar to the eukaryotic protein Src
any gene in a healthy cell capable of promoting tumor growth--> proto-oncogene
48
Tumor Suppressor
RB1
Most tumor suppressors can be expressed from either chromosome, and will need to be homozygous deletion/mutation
Heterozygous mutations can be inherited and families show increased susceptibility to cancers
Also called "loss of heterozygosity"
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Genetic Basis of Cancer
Cancers often take 20 years or more to develop, although the time to cancer is decreased with increased mutation rate, such as through exposure to carcinogens
Carcinogen-induced cancers have very high mutation rates
50
Targeting Oncogenic mutations
Activating mutations can predict susceptibility to targeted therapy
15-30% of NSCLC patients have an EGFR mutation
Mutations can be identified using sequencing technologies
Mutations in EGFR catalytic domain increase the intensity and duration of signaling in response to logand
51
Tumor Suppressor Mutations
Loss of function mutations can predict susceptibility to chemotherapies
"Synthetic lethality"
Kill tumor cell while keeping healthy tumor in tact
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BRCA 1 and BRCA2
Tumor suppressors
The BRCA1 and 2 gene encode for proteins involved in DNA repair
The nonfunctional mutant alleles of BRCA1/2 are inherited as germline mutations
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BRCA mutations in breast cancer increase susceptibility to PARP inhibitors
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Olaparib
PARP inhibitor: binds to DNA when it is bound it recruits additional modifiers
For cancers with BRCA1/2 mutations it works by "trapping" PARP DNA--> unable to uncouple from DNA
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Chemotherapy
target the central dogma
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G0/G1
Cell is quiescent or accumulating building blocks required for division
CDK 4/6
G1: kinase inhibitors and hormone inhibitors
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S
cell replicating DNA
CDK1
Anti-metabolites, Antifolates, Topol inhibitors
58
G2
Cell assembling machinery for chromosomal segregation and cytokinesis
Topo2 inhibitors
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M
mitosis
chromosome segregation
Microtubule inhibitors
60
R-point
restriction point is the critical time point when cells decide whether or not to enter the cell cycle
61
G1 to S
Is there a signal telling cell to proceed through cycle?
Are there sufficient quantities of the required nucleotide "building block?"
Is there unrepaired DNA damage?
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S to G2
Has the genome been replicated?
Are there any errors?
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G2 to M
Have sister chromatid arms been separated?
Has the machinery required for chromosomal segregation and cytokinesis been assembled?
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P16
Tumor suppressor
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TP53
Tumor suppressor
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RAS
Oncogene
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Palbociclib
Cdk4/6 kinase inhibitor
Aren't exactly "targeted therapy" because they target all replicating cells
Adverse reactions: neutropenia, nausea, fatigue, diarrhea, vomiting
Approved for cancers arising due to BRCA1/2 mutations
68
When normal cells are exposed to certain chemotherapy drugs that cause DNA damage
cells halt in G1 until DNA repaired
cells then proceed into S
If cells proceed into S without repairing DNA, they apoptose
preserves genomic integrity of daughter cells
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When tumor cells that have lost G1/S checkpoint control are treated with chemotherapy that causes DNA damage
Cells don't halt in G1 and attempt to replicate damaged DNA
Attempting to replicate damaged DNA can trigger apoptosis
OR, if the apoptotic response has been lost cells replicate damaged DNA and acquire lethal genetic damage that results in necrosis
70
Drugs that are more effective against cycling cells at many phases of the cell cycle are called cell cycle non-specific
These drugs are more effective when the tumor cells are progressing through the cell cycle, but they are not dependent upon the cell being in a specific phase of the cycle
Alkylating agents and DNA intercalation agents
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Phase-specific
drugs are most effective against tumor cells in a specific phase of the cell cycle
DNA synthesis (S phase) or Mitosis (M phase)
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Major dose-limiting toxicities of chemotherapy
Hematopoietic: WBC-infections, platelets-hemostasis, RBC-anemia
Gastrointestinal, N/V, loss of appetite
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Combination chemotherapy
use combinations of drugs each of which is at least partially effective against a particular tumor
a drug that is ineffective when used alone is often not approved for combination studies, although this is changing
individual drugs in combination should be used at max doses
use drugs with different mechanism of action or different cell cycle specificities
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CHOP
C: cyclophosphamide
H: Doxorubicin
O: Vincristine
P: Prednisone
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Drug resistance
Many tumors initially sensitive to chemotherapy become resistant
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Changes in drug targets/function
increased expression of drug target through gene amplification
emergence of a mutant, structurally altered target
emergence of cells with alterations in genes where the downstream effects are functionally redundant with the drug target
cells can rewire the pathway to bypass the need for drug target
