Lecture 39 Anticancer therapies radiation and drugs for cancer Flashcards
1
Q
What are the key properties of a cancer cell?
A
- they reproduce without regard to normal restraints on cell growth and cell division
- they invade and colonize areas normally reserved for other cells
2
Q
Do all cancer cells metastasize?
A
- no
3
Q
When are tumors considered benign?
A
- if the neoplastic cells do not become invasive
4
Q
When are tumors considered malignant?
A
- if it acquires ability to invade surrounding tissue
5
Q
What is a consequence of malignant tumors invasiveness?
A
- they produce cells that break out of their primary site and form secondary tumors at other sites
6
Q
What are the sites where secondary tumors are formed?
A
- metastases
7
Q
Is a single mutation enough to cause cancer?
A
- no
8
Q
What are potential risk factors for cancer?
A
- radiation exposure
- UV light from the sun
- chemicals (carcinogens)
- life-style (smoking, certain diets)
- Viruses (EBV, HIV, HPV)
9
Q
Where are the most common cancers of epithelia?
A
- reproductive tract
10
Q
Why does the risk of cancer increase with age?
A
- the longer you live the more likely you are to develop a second hit or exposed to a cancer causing environment
11
Q
If you are exposed to 2-naphthylamine more than 5 years what happens?
A
- onset of cancer was earlier
- and risk increases
12
Q
Duration of exposure does what?
A
- increases risk and influences time of onset
13
Q
What is p53 key in?
A
- a key mechanism in the cellular response to DNA damage
14
Q
If DNA damage is a critical determinant of progression to next stage, what protein is involved?
A
- p53 involved
15
Q
What does Mdm2 lead to?
A
- p53 being ubiquinated and degraded
16
Q
What happens after DNA damage in cell cycle?
A
- DNA damage
- Phosphorylation
- Mdm2 removed
- P53 binds to p21 (Cdk inhibitor)
- Cdk inhibitor translated and shuts down G1/s-cdk and S-cdk
17
Q
What is p21?
A
- a cdk inhibitor that is translated once p53 binds to its transcription factors
18
Q
What happens is p53 doesnt function properly?
A
- wont have brake that happens when there is DNA damage
19
Q
What is p53?
A
- tumor suppressor
20
Q
What is the basic strategy for cancer treatment drugs?
A
- to induce so much damage to tumor cells via DNA damage that they cant divide
21
Q
What are the side effects of cancer treatment drugs?
A
- they can have the same effects on non cancer cells
22
Q
What is external beam therapy?
A
- uses a machine to send high energy beams from outside the body to the tumor area
23
Q
What is internal radiation therapy?
A
- radioisotope given internally, radiation generally only travels a short distance depending upon the isotope and its energy
24
Q
What treats thyroid tumors?
A
- iodine therapy
internal radiation therapy
25
How does photon therapy work?
- works either by direct ionization of atoms in the DNA chain or indirectly by ionization of water to form hydroxyl radicals that can then damage DNA
26
What does charge particle or proton therapy do?
- uses a particle accelerator to beam high-energy particles (protons or carbon, boron or neon nuclei)
27
What is an advantage of proton therapy?
- better ability to precisely localize the radiation dosage and less damage to surrounding healthy tissue
28
How does doxorubicin work?
- doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis
29
What is another way doxorubicin works?
- forms oxygen free radicals resulting in secondary cytotoxicity
30
What does bleomycin do?
- forms complexes with iron that reduce molecular oxygen to superoxide and hydroxyl radicals which cause single and double stranded breaks in DNA
31
How does cisplatin work?
- inorganic platinum agent
- forms highly reactive platinum complexes which bind to nucleophilic groups such as GC-rich sites in DNA
- inducing intrastrand DNA cross links as wells as DNA protein cross links
- these cross links result in apoptosis and cell growth inhibition
32
What is a side effect of cisplatin?
- kidney toxcity
33
What does methotrexate do?
- inhibits the enzyme dihydofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis and subsequently inhibition of RNA syntheses.
34
On a simpler level how does methotrexane work?
- rate limits purine nucleotide synthesis
| - dont have building blocks for DNA
35
How does vinblastine work?
- vinblastine binds to tubulin and inhibits microtubule formation
36
What does no microtubule formation result in?
- disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of cell cycle
37
What does vincristine?
- interferes with mitotic spindle in S phase of cell cycle
| - leaves tumor cells in metaphase
38
What does prednisolone do?
- it binds to and activates specific nuclear receptors resulting in an altered gene expression and inhibition of proinflammatory cytokine production
- induces apoptosis
- longterm use has affects on other cells like osteocytes
39
Where do we get many of these cancer drugs?
- plants
40
What is prednisolone typically used for?
- it is a synthetic glutocorticoid with anti-inflammatory properties
41
How is prednisolone used as an anti-cancer drug?
- it binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production
- also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates APOPTOSIS
42
What is immunotherapy?
- a treatment designed to induce enhance or suppress the immune response
- designed to stimulate a persons own immune response to destroy cancer cells
43
What has been shown to help shrink or slow growth of tumors such as melonoma, non-small cell lung cancer, and hodgkin lymphoma?
- opdivo and kytruda
44
What do opdivo and keytruda target?
- PD-1 on T-cells
45
What is PD-1?
- is a part of an immune checkpoint checkpoint control system that keeps immune cells from attacking self
46
What is leukemia?
- an overgrowth of WBCs
47
What is chronic myelogenous leukemia caused by?
- a chromosomal translocation called the philadelphia chromosome
48
What does the translocation on the philadelpia chromosome create?
- a fusion gene/protein between the BCR gene and ABL gene
49
what type of fusion protein is the philadelphia chromosome?
- a tyroskine kinase
50
What is leukemia characterized by?
- increased production/growth of myeloid cells in the bone marrow that then circulate in the blood
51
What is the parent drug used to treat CML?
- gleevec
52
What is the mechanism of Bcr-Abl gene formation?
- bcr breaks at 5' end
- abl breaks near 5' to 3' end
- translocation
- transcription to fused Bcr/Abl mRNA
- translation to Bcr-Abl fusion protein
53
What is the first phase of treatment for leukemia?
- induction therapy
54
What is the goal of the induction phase?
- to kill the luekemia cells in the blood and bone marrow and put leukemia into remission
55
What is the second stage of luekemia treatment?
- consolidation/intensification
56
When does the consolidation phase begin?
- once the luekemia is in remission
57
What is the goal of the consolidation phase?
- to kill any remaining leukemia cells that might not be active but could begin to regrow and cause a relapse
58
What is the last phase of treatment?
- maintenance therapy
59
What is the goal of maintenance therapy?
- to kill any remaining luekemia cells that may regrow and cause a relapse
60
When are the cancer treatments given in lower doses?
- the maintenance therapy phase
61
Does acute myeloid luekemia have a spectrum?
yes
62
What are the subtypes of AML based off of?
- they are based upon the cell that the luekemia develops from and many chromosomal translocations that create fusion proteins
63
What is the easiest form of AML to treat?
- AML M3
64
What is a dangerous side effect of AML 3?
- patients can develop blood-clotting and bleeding problems
65
What mutation leads to AML3?
- a translocation of the retinoic acid receptor alpha gene (RARA) on Cs17 with the PML gene on Cs15
66
What does PML-RARA fusion preotein do?
- it has an altered function
| - it binds with high affinity to sites on the DNA important for granulocyte differentiation
67
What does the blocking of differentiation lead to from the PML-RARA fusion protein?
- it leads to immature leukemic promyelocytes
68
How does ATRA treat the PML-RARA fusion protein?
- it induces the promyelocytes terminal differentiation and then these differentiated malignant cells undergo apoptosis
- ATRA induces dissociation of NCOR and HDAC allowing for differentiation to proceed
69
What does Acute Lymphoblastic Leukemia do?
- bone marrow produces too many immature lymphocytes (at the expense of other blood cell types)
- expense of ALL
70
What are the risk factors of ALL?
- exposure to x-rays before birth
- exposure to radiation
- past treatment with chemotherapy
- certain changes in the genes
- genetic conditions that include down sydrome, and bloom syndrome
71
What are some signs and symptoms of ALL?
- fever, foul smelling urine, easy bruising or bleeding, petechia, bone or joint pain, lumps in neck
72
How would you diagnose a patient with ALL?
- blood CBC, bone marrow analysis, cytogenetic analysis
73
What is an important prognosis of ALL?
- the number of WBC at diagnosis
74
Can ALL spread to the CNS?
- yes that is why intrathecal treatment is so important
75
Where do most relapses of ALL come from?
- spinal fluid
76
If a child is 1-10 years old and have a WBC of less than 50,000 they are considered ____ risk?
- low
77
If a child is 1-10 years old and have a WBC of 50,000 or more at diagnosis are considered ______ risk?
- high
78
What drug treatment for water would make a child chunky and retain water?
- prednisolone
