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BSCI433: Biology of Cancer > Lecture 7: Multi-Step tumorigenesis & Metastasis > Flashcards

Lecture 7: Multi-Step tumorigenesis & Metastasis Flashcards

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1
Q

Primary Site

A

Term to describe the original, first tumor in the body

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2
Q

Staging

A

Refers to the grouping of patients according to the extent of their disease

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3
Q

Metastatic Cancer

A

When primary cancer disseminates to other organs and forms a new, secondary tumor that will be the same type as the primary tumor

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4
Q

As of 2019, cancer is the ______ leading cause of death in the United States behind ____________, and the majority of patients who die of cancer, die of __________.

A

Second
Cardiovascular disease
Metastases

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5
Q

Transplacental transmission of malignant cells is rare. Metastatic disease appeared at birth to ______ months of age at least _________% of patients have died from metastatic tumors.

A

20

65%

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5
Q

Cancer Stage

A

Staging is a description of the gross appearance of the tumor including size, invasion, spread to local sites & lymph nodes, or metastasis.

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6
Q

Cancer Grade

A

Grading is a description of the microscopic appearance of the tumor’s cells and tissue.

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7
Q

TNM Abbreviation

A

T: Size & extent of the main primary tumor
N: Number of nearby lymph nodes containing cancer cells
M: Whether the cancer has metastasized.
(Tumor, Node, Metastasis)

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8
Q

TNM System

A

System for classifying a malignancy to provide information about the anatomic extent of invasion and tumor size.

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9
Q

T1 in TNM System

A

Less than 2 centimeters

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10
Q

T2

A

2-5 Centimeters

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11
Q

T3

A

Greater than 5 centimeters

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12
Q

T4

A

Tumor over 5 centimeters

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12
Q

TX

A

Tumor can not be measured

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13
Q

T0

A

Tumor cannot be found

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14
Q

NX

A

Cancer in the nearby lymph nodes cannot be measured

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15
Q

N0

A

There is no cancer in the nearby lymph nodes

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16
Q

N1,N2, N3

A

Number and location of lymph nodes that contain cancer. The higher then N, the more lymph nodes contain cancer.

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17
Q

MX

A

Metastasis cannot be measured

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18
Q

M0

A

Cancer has not spread to other parts of the body (No metastasis)

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19
Q

In situ

A

Abnormal cells present but have not spread to nearby tissue

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20
Q

M1

A

Cancer has spread to other parts of the body (Metastatic)

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21
Q

Localized

A

Cancer is limited to the place where it started, with no sign it has spread

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22
Q

Regional

A

Cancer has spread to nearby lymph nodes, tissues, or organs

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23
Q

Distant

A

Cancer has spread to distant parts of the body

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24
Q

Unknown

A

Not enough information to figure out the stage

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25
Q

Skin metastasis from internal organs has a _________ to ______% incidence and ________ metastasis is much rarer.

A

5-10%

Zosteriform

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26
Q

Probable mechanism for band-distributed skin metastasis

A

The retrograde flow of lymph after obstruction by cancer cells

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27
Q

Mechanism of inflammatory breast cancer

A

Cancer cells block the smallest lymph package of the breast

28
Q

Breast-Conserving surgery

A

Removes cancer while leaving as much normal breast as possible

28
Q

Tumor Grade

A

Description of tumor based on histology: How abnormal the tumor cells and the tumor tissue looks under a microscope

29
Q

“Well differentiated”

A

When the cells of the tumor and the organization of the tumors tissue are close to those of normal cells and tissue. These tumors grow and spread at slower rates

30
Q

“Undifferentiated” or “Poorly Differentiated”

A

Tumors have abnormal looking cells and may lack normal tissue structures. These tumors grow faster and are closer to becoming metastatic

31
Q

Grade 1

A

Well Differentiated (Low Grade): Cancer cells that resemble normal cells and aren’t growing rapidly

32
Q

Grade 2

A

Moderately differentiated (Intermediate grade): Cancer cells that don’t look like normal cells and are growing faster than normal cells

33
Q

Grade 3

A

Poorly Differentiated (High grade): Cancer cells that look abnormal and may grow or spread more aggressively

34
Q

Grade 4

A

Undifferentiated (High grade): Tumor cells look most abnormal

35
Q

TP53

A

Tumor marker capable of improving prognosis accuracy. In endometrial endometrioid carinoma, reclassified G1/2 from low grade to high grade

36
Q

MSK-IMPACT

A

Identified actionable genetic changes in 37% of patients with advanced solid cancers

37
Q

Actionable Mutation

A

One that can be targeted with either an approved drug or one being tested in clinical trials

38
Q

Non-cancer deaths among patients who live with metastatic cancer may largely be divided into 2 groups

A
  1. Chronic comorbid conditions
    2/ Acute, iatrogenic, or treatment-induced infections
39
Q

Mutation requirements for cancer

A
  1. 1-10 mutations needed
  2. Half of the coding driver mutations occur outside of known cancer genes
  3. Genomic instability is a cornerstone of cancer
40
Q

Driver Mutations

A

Mutations that provide growth advantage and promote cancer development

41
Q

Passenger mutations

A

Those that do not provide growth advantage or promote cancer development

42
Q

Most mutations in driver genes that were shared between primary and metastatic tumors were predicted to have __________

A

Functional consequences

42
Q

Within individual patients, a large majority of driver gene mutations are common to _____ metastases

A

All

43
Q

6 Cascading process of metastasis

A
  1. Epithelial to mesenchymal transition (EMT)
  2. Invasion to surrounding tissue
  3. Intravasation to blood vessels
  4. Survival in circulation
  5. Extravasation to colonize and thrive at distant sites
  6. Organotropism/Organ-specific metastasis
43
Q

Studies such as Lee-Fraumeni patients and mutant p53 knock-in mice provide a strong case for p53 mutations acting as the ___________ for tumorigenesis

A

Initial driving force

43
Q

Tumor suppressors are driver genes in which driver mutations are ______

A

Inactivating

44
Q

Liver metastasis occurs in ________% of adults dying of cancer

A

40-50%

45
Q

Oncogenes are definted as driver genes in which driver mutations are ___________ or result in new functions

A

Activating

46
Q

____________ rather than the age at which exposure began determines likelihood of developing a detectable tumor

A

Cumulative exposure

46
Q

The ________________ has _________ which allow malignant to escapes circulation and enter liver parenchyma

A
  1. Sinusoidal epithelium
  2. Fenestrations
47
Q

Multistep tumorigenesis

A

Histopathological progression from normal cells to cancer cells
1. Hyperplasia
2. Adenoma/Dysplasia
3. Carcinoma
4. Metastasis

48
Q

LOH in colon tumor progression

A

Early adenoma often has LOH in the long arm of chromosome 5

49
Q

CIS

A

Carcinoma in situ

50
Q

Almost half of slightly larger adenomas carried, in addition, a ______ _______ oncogene

A

mutant k-ras

50
Q

DCIS

A

Ductal carcinoma in situ

50
Q

CIN

A

Cervical intraepithelial neoplasia

50
Q

Around half of all carcinomas showed an ______ on the short arm of chromosome ______

A

LOH
17

51
Q

Larger adenomas tend to have high rates of LOH on the long arm of chromosome ________

A

LOH
18/18q

52
Q

PIN

A

Prostatic intraepithelial neoplasia

53
Q

Genomes of most evolving, pre-neoplastic growths were found to suffer widespread _____

A

HYPOmethylation

54
Q

Consequences of hypomethylation

A

Chromosomal instability

55
Q

Aberrant crypt foci often carry an ___________________ together with an activated _______ oncogene

A
  1. Inactivated APC tumor supressor gene
  2. K-ras
56
Q

At the primary tumor site, a tiny fraction of long term self renewing ___________ may represent early MICs with driver mutations and high cellular plasticity

A

Tumor-initiating cells (TICs)

57
Q

Epithelial-mesenchymal plasticity of metastatic cells

A

Acquisition of stem cell-like properties

58
Q

Metabolic reprogramming of metastatic cells

A

MICs may require a high metabolic adaptability and metabolic stress resistance. Different host organs also have different nutrients and oxygen conditions

59
Q

Hypoxia inducible factor-1 (HIF-1)

A

Factor activated by metastatic breast cancer cells in bone go survive hypoxia and increased angiogenesis

60
Q

Resistance to apoptosis & upregulation of anti-apoptotic pathway of metastatic cells

A

High expression of anti-apoptotic proteins such as Bcl-xL and Bcl-2

61
Q

Organotropism

A

Non-random distribution among distant organs

62
Q

Factors regulating organotropism

A

-Circulation pattern
-Tumor-intrinsic factors
-Organ specific niches
-Interactions between tumor cells and host micro environment

BSCI433: Biology of Cancer (21 decks)

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