Chemotherapy Flashcards
What is metastasis?
abnormal cell growth with potential to spread to other parts of the body
What causes cancer?
- environmental factors (e.g. tobacco, radiation, pollution)
- viral infections (e.g. HIV)
- genetics (e.g. BRCA1 in breast cancer)
What is cancer defined as, in terms of disease? Based on this definition, how does cancer arise?
cancer = disease of cell growth REGULATION
cancer arises when GENES that regulate cell growth are MUTATED
What occurs to a cancer cell when there is unfixable DNA damage?
a) apoptosis
b) cell continues dividing
b) cell continues dividing
What occurs to a normal cell when there is unfixable DNA damage?
a) apoptosis
b) cell continues dividing
a) apoptosis
What are all the phases of the cell cycle?
1) G1 phase: checkpoint to ensure cell is ready for DNA synthesis
2) S phase: DNA synthesis
3) G2 phase: checkpoint to ensure cell is ready for mitosis
4) M phase: mitotic phase (cell divides into 2 daughter cells)
5) G0 phase: quiescent state
What are the 2 groups of genes important for regulation of the cell cycle?
1) tumor suppressor genes (and the proteins they encode)
2) oncogenes
What is the overall goal/function of tumor suppressor genes? What are some mechanisms to achieve this goal?
function: repress cell cycle/promote apoptosis
mechanisms:
1) inhibit cell division
2) initiate apoptosis following DNA damage
3) DNA repair proteins
What is p53?
tumor suppressor protein that regulates the cell cycle
p53 is mutated in __ % of all tumors
50%
What is the difference between proto-oncogenes and oncogenes?
proto-oncogenes = normal genes involved in cell growth and proliferation or inhibition of apoptosis (i.e. opposite of tumor suppressor genes)
oncogenes = cancer genes due to mutations that can increase expression
what are the 2 types of mutations that can cause oncogenes to form? define them.
1) point mutations = small-scale deletions or insertions which affect its expression
2) chromosomal translocation = 2 separate chromosomal regions become abnormally fused
What is the Philadelphia chromosome? what kind of cancer cells is this chromosome found in? This chromosome leads to unregulated expression of which protein?
- an oncogene
- abnormal chromosome 22 (translocation of chromo 9 and 22)
- found in LEUKEMIA cancer cells
- fusion –> new gene –> BCR-ABL (BCR gene from 22 and ABL from 9)
- unregulated expression of TYROSINE KINASE ACTIVITY
TRUE or FALSE: Usually, MULTIPLE oncogenes and tumor suppressor genes will act in concert to cause cancer.
TRUE
1/3 of cancers can be cures with local treatment (surgery and radiotherapy); however, anti-cancer drugs are required in other cases. Why are anti-cancer drugs used instead of local treatment?
anti-cancer drugs address metastasis
When diagnosed at an advanced stage, anti-cancer drugs alone cure less than ___% of cancer patients.
10%
TRUE or FALSE: Normal tissues that proliferate rapidly (bone marrow, hair follicles, intestinal epithelium) are susceptible to damage from cytotoxic anti-cancer drugs.
TRUE
e.g. hair loss from chemotherapy
Which 2 phases of the cell cycle do MOST anti-cancer drugs interfere with?
S phase and M phase
What are 4 types of DNA Synthesis Inhibitors used to treat cancer?
1) pyrimidine analogues
2) purine analogues
3) alkylating agents
4) anti-folates
What are pyrimidine analogues? What are the nucleoside bases used? What is the mechanism? Provide an example drug and its mechanism.
- DNA synthesis inhibitor
- DNA bases = T and C; RNA bases = U and C
- mechanism: compete with normal pyrimidine precursors for the enzyme THYMIDYLATE SYNTHASE (changes dUMP to dTMP)
- drug: 5-FLUOROURACIL (5-FU)
- 5-FU mechanism: must be activated to FdUMP to act as a pyrimidine analogue
What are purine analogues? What are the nucleoside bases used? What is the mechanism? Provide an example drug and its mechanism.
- DNA synthesis inhibitor
- DNA and RNA bases = A and G
- mechanism: rate-limiting facto for purine synthesis (alter synthesis and function of RNA and DNA)
- drug: 6-MERCAPTOPURINE
- drug mechanism: inhibit enzyme PHOSPHORIBOSYL PYROPHOSPHATE AMIDOTRANSFERASE (PRPP amidotransferase) –> inhibit purine nucleotide biosynthesis and metabolism
What is an alkylating agent? What is the mechanism? Provide an example drug and its mechanism.
- DNA synthesis inhibitor
- mechanism:
highly reactive compounds –> covalently link to chemical groups found in nucleic acids –> these modified nucleic acids cross-link between DNA strands –> lead to strand breakage - drug: CISPLATIN
- drug mechanism: platinum analogue –> lead to cross links –> strand breakage
What atom of guanine is most susceptible to formation of covalent bond with alkylating agents?
N7
Which 2 phases of the cell cycle are most susceptible to alkylating agents?
(hint: alkylating agents are DNA synthesis inhibitors)
G1 and S
