Cancer Basics Flashcards
What is cancer?
Diseases characterized by abnormal regulation of cell growth and reproduction
___ and ___ lead to unregulated and increased cell proliferation
Damage and changes in gene expression
What do cancer cells compete with normal cells for?
Space and nutrients
Cancers increased population of unregulated cells have the capacity to ___ and ___ others
travel and invade
Name the 2 steps of the cell cycle.
Interphase and mitotic phase
Where are the cell checkpoints and what is their function?
G1(stops duplication if DNA is damaged) and G2(stops cycle if damaged
What are the three parts of interphase?
G1-Cell growth, S-Cell growth and DNA synthesis, G2- Growth and prep for division
What happens during the mitotic phase? What is the breakdown of stages within the mitotic phase?
Split into two identical daughter cells. PMAT(prophase, metaphase, anaphase, telophase)
What does cytokinesis signify?
Complete division
What cells reproduce rapidly? Provide example
Bone marrow or skin cells
What cells never reproduce? Provide example
neurons
For the cells that don’t reproduce, what stage are they thought to remain in?
G0
What is the Retinoblastoma pathway?
A complex signaling system controlling division
Is the RB pathway a major target for human cancer-causing mutations?
yes
Where does the most common mutation occur(in regards to the cell cycle/checkpoints)?
The most common effects the G1 checkpoint via mutation of the RB pathway
What is cyclin D?
A protein which binds to RB protein causing E2F to unbind
When E2F unbinds from RB, what is the result?
Becomes inactivated, allowing it to progress through the cell cycle
What 3 primary mutations can occur at the RB pathway?
1) Mutation can occur on RB, keeping it inactive indefinitely
2) Mutation can occur on transcription factor E2F, causing an under-expression, resulting in inactivation of RB and therefore progression through the cell cycle
3) Over-expression of cyclin D can lead to more inactivation of RB than normal, allowing for the cell to progress through the cell cycle.
Describe the status of RB activation/inactivation and how cyclin D and E2F influence it.
RB is active when E2F is bound to it. Active means that it is not able to pass the G1 checkpoint or continue with the cell cycle. If cyclin D is expressed, it binds to RB, unbinding transcription factor E2F and inactivating the protein. This allows the cell to pass the G1 checkpoint, whether damaged or not, and continue the cycle.
TorF: Any alteration that occurs at the RB pathway which inactivates RB can lead to cancer.
True
What are other possible regulation issues in cancer cells? (There are 4)
1) presence of growth factors
2) Ratio of cell surface area to cell volume
3) Contact inhibition limiting cell growth due to lack of space
4) Cell growth inhibition due to a collection of the cell’s own secretions
What is carcinogenesis?
The process by which a normal cell becomes cancerous
What are the steps of carcinogenesis?
Initiation and Promotion
What is the initiation portion of carcinogenesis?
The carcinogen attacks a normal cell
What is the multiple hit theory?
Two hits are required to mutate a gene. The first hit could be hereditary, in which it was passed down. The first hit could also be due to a rare event (carcinogen). The second hit would be a rare event (carcinogen) in which that gene becomes mutated. Therefore, all daughter cells from this mutated gene will then produce mutated genes.
What is the promotion portion of carcinogenesis?
The gene is expressed within the cell causing uncontrolled division and tumor production
Can a cell have one hit and still be functioning normally?
yes
What two types of genes are mutated and lead to cancer?
Oncogenes and Tumor suppressor genes
What do oncogenes do when mutated?
Oncogenes gain a function when mutated, allowing them to ignore normal signals which would limit cell growth or cause apoptosis
What do tumor suppressor genes do when mutated?
Tumor suppressor genes lose function when mutated.
What is an example of a mutated tumor suppressor gene and what would be the result?
If p21 were to be mutated, it could lose the normal function of blocking cyclin D, and would allow cyclin D to inactivate the RB protein and go past the checkpoint.
What 3 oncogenes are mentioned?
HER2, Ras and Myc
What Tumor suppressor genes are mentioned?
RB, p16/p21, p53, BRCA1/BRCA2
If E2F is bound to RB, what is the result?
This activates RB and will not allow the cell cycle to progress. This allows for time to destroy itself(apoptosis) or heal if damaged.
What happens if cyclic D is expressed and binds to RB?
This inactivates RB, allowing it to go beyond the checkpoint, allowing cell cycle progression
Which part of the RB pathway, if mutated, will lead to unregulated cell growth?
Any part
If RB is mutated, what could be the result?
It could remain inactivated on its own, allowing for cell cycle progression
If E2F is under-expressed due to mutation, what will result?
E2F would not be available to be bound to RB, leaving it inactivated and able to pass the checkpoint for cell cycle progression
If cyclin D is over-expressed, what would be the result?
Cyclin D would be readily available to bind to RB, resulting in inactivation of RB and allowing it to pass the checkpoint for cell cycle progression
If a tumor suppressor gene is mutated, what would be the result?
Mutation to the tumor suppressor cell would lead to loss of function, resulting in cyclin D binding to RB and inactivating it. This would allow RB to pass the checkpoint for cell cycle progression.
What abnormalities can cancer cause in general?
Lack of appropriate signal response which control growth, loss of cell differentiation, decreased drug sensitivity, increased invasiveness throughout the body
What is a tumor?
A mass of abnormal cells
What does it mean if a tumor is benign?
It is usually harmless, slow growing and consists of well organized cells
What does it mean if a tumor is malignant?
It is harmful, having the ability to kill the host tissue unless removed. Loss of differentiation among cells
Are malignant tumor cells programmed for proliferation?
yes
What effect would tumor cells have on the architecture of an invaded organ?
It could destroy the normal architecture, impeding the normal function
Tumor cells can cause large areas of necrosis, what does this mean?
Due to the lack of blood flow and/or apoptosis, death of cells within a tissue or organ.
What does tumor grade really look at?
How the tumor cells look under a microscope.
What is observed when determining a tumor grade?
Cell differentiation and growth rate
What are the tumor grades?
Grade X, Grade 1-4
Which tumor grade would result from undifferentiated cells?
Grade 4
Which tumor grade would result from well differentiated cells?
Grade 1
What tumor grading is available for prostate, breast and kidney cancers?
Prostate: Gleason
Breast: Bloom-Richardson
Kidney: Fuhrman
What does cancer grade look at?
Severity and likelihood that the cancer will grow/spread
What is the TNM system? What does each letter stand for?
The TNM system is a way to stage cancer. It looks at the tumor size (T), number of lymph nodes involved (N) and the presence/absence of metastasis (M)
How many stages of cancer are there?
4
What are the characteristics of a stage 1 cancer?
It is limited to the organ of origin, <2 cm, no lymph involvement and no metastasis
What are the characteristics of a stage 2 cancer?
Local spread into surround tissues, 2-5 cm, No OR same side lymph involvement and no metastasis
What are the characteristics of a stage 3 cancer?
Extensive primary lesions w/ fixation to deep structures and lymph node invasion, >5 cm, lymph node involvement on same side, no metastasis
What are the characteristics of a stage 4 cancer?
Distant metastasis present, size and lymph node involvement do not matter
What are the liquid cancers?
Leukemia and Lymphoma
Does leukemia utilize the TNM system?
No, they look at cellular classification
Does lymphoma utilize the TNM system?
No, but 5 factors are used to determine risk with the international prognostic index. These include the age(>60), stage of lymphoma (3 or 4), spread to organs outside of lymph system, ability to complete ADLs, blood serum levels of lactate dehydrogenase(increased with the amount of lymphoma present). Each of these is given one point which corresponds to a relative risk
Using the International Prognostic Index, describe the point: risk stratification: 5 year survival %.
0-1: Low: 73%
2 :Low to intermediate: 51%
3: Intermediate to high: 43%
4-5: High risk: 26%
What determines the name/ type of cancer?
It is named according to tissue or organ of origin and the degree of differentiation.
Describe a carcinoma
Solid tumor originating in epithelial lining. Most common (85-90%). Most treatable
Describe a sarcoma
Solid tumor originating in connective tissue. Rarest (<2%)
Describe leukemia
Abnormal WBC production in bone marrow ~2%
Describe lympoma
Developed within a lymph gland. ~5%
Describe CNS cancers
Brain and spinal cord tissue origin. ~1%. ~33% survival rate
