Oncology Flashcards
(138 cards)
1
Q
What are the 8 hallmarks of cancer
A
- Sustained angiogenesisi
- Evading apoptosis
- Self sufficiency in growth signals
- Insesntitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Deregulating cellular metabolism
- Immune evasion
2
Q
What is the role of oncogenes and tumor supressor genes?
A
- Overactive tumor promoting genes (oncogenes) - caused by mutation to proto-oncogene, required mutation in one allele (dominant)
- Loss of tumor supressor genes - requires loss of both alleles (recessive)
3
Q
What is the role of P53
A
- Acts as a checkpoint gene to survey cellular DNA damage
- Stops cell division when significant DNA damage is detected
- Can trigger apoptosis
- Loss of P53 is most common genetic alteration in human cancers
4
Q
What is epigenetics?
A
- Gene function alteratiosn without changes to the DNA
- Usually through changes in the regulatory elements (promotor or enhancer)
- Linked to environemntal and acquired cancer risks
5
Q
What are telomeres
A
- Specialised DNA protein complexes which cap chromosome ends and maintain stability
- Tandem repeats of TTAGGG
- Telomeres shorten with each division
6
Q
What is telomerase
A
- Telomerase is a reverse transcriptase which extends telomeres giving cells proliferative potential
- Cancer cells often have high telomerase levels
7
Q
What are the 5 steps in the metastatic cascade?
A
- Cellular basement membrane invasion and migration
- Invasion of nearby vessels and lymphatics
- Survival in circulation
- Extravasation into new tissues
- Proliferation in new site
8
Q
What is angiogenesis (in neoplasia) and what are some of the growth factors that contribute to it
A
- Formation of new blood vessels within the tumor micorenvironment
- Driven by: Hypoxia, VEGF (vascular endothelial growth factor), PDGF (platelet endothelial growth factor) and bFGF (basic fibroblast growth factor)
- Many cancer cells can induce angiogenesis in absence of hypoxia by upregulating stimulatory cytockines
9
Q
What is the cancer stem cell hypothesis?
A
- This proposes there is a population of cells within tumors that account for the rapid recurrence of a cancer after initial response to therapy.
- These cells are: slowly dividing, self renewing, resistant to conventional treatment.
10
Q
Chemotherapy is most effective against small tumor burdens - due to what biological factors?
A
As tumors grow:
- growth fraction decreases
- cell time increases
- heterogenicity increases (leading to spontaneous resistance)
- areas of poor drug perfusion develop
11
Q
Name some alkylating agents and their broad mechanism of action
A
- Cyclophosphamide, chlorambucil, melphalan, lomustine (CCNU)
- Create cross-links in DNA causing strand breaks or DNA alkylation
12
Q
Name some antitumor antibiotics (anthracyclines) and their broad mechanism of action
A
- Doxorubicin, epirubicin, mitoxantrone
- Intercalate DNA and interfere with topoisomerases
- Are substrates for the multidrug resistance (MDR) pump (risk of resistance)
13
Q
Name some Mitotitc inhibitors and their broad mechanism of action
A
- block spindle assembly (vinca alkaloids - vinblastine, vincristine, vinorelbine)
- or spindle stability (paclitaxel)
14
Q
Name some platinum agents and their broad mechanism of action
A
Cisplatin, carboplatin
Create DNA cross-links and strand breaking
15
Q
Name some antimetabolite agents and their broad mechanism of action
A
- Rabacfosadine, gemcitabine, Cytosine arabinoside, methotrexate, 5FU
- Nuceloside analogues or DNA enzyme inhbitors
- Interfere with DNA synthesis
16
Q
What are the aims of a combination chemotherapy protocol
A
- Target different tumor cellular metabolic pathways to overcome resistance
- Maintain effectiveness without compounding toxicity
- Avoidance of cross-resistance
17
Q
What is the mechanism of action of radiotherapy
A
Damages DNA
- Photons cause direct ionisation (1/3)
- non-DNA ionisation caused by free radicle ionisation (2/3)
- Cause strand breakage - DSB (double strand break) most effective for cell death
18
Q
What are the 5 R’s in radiation biology
A
- Repair: Radiation induces more repairable breaks than non-repairable, fractionation takes advantage of this
- Redistribution: Fractionation allows cells to move between cycle phases of varying sensitivity
- Repopulation: Tumour cells can regenerate during treatment (a common cause of failure)
- Re-oxygenation: Fractionation improves oxygenation of hypoxic tumour areas, oxygenation of tissues improves effect of radiation
- Radiosensitivity: Different cells have different radiosensitivity
19
Q
Which immune cells are responsible for direct tumor cell killing
A
CD 8+ and NK cells
20
Q
What is the mechanism of action of toceranib
A
A multikinase inhibitor that acts on multiple receptor tyrosine kinases (RTKs)
* Direct action: inhibiting transmitting KIT signals with gain-of-function mutations.
* Indirect action: controlling angiogenesis through PDGFR and VEGFR inhibition
* It induces regulatory T cell suppression.
21
Q
What are 3 main targets of toceranib
A
KIT,
Vascular endothelial growth factor receptor 2 (VEGFR2),
Platelet-derived growth factor receptor (PDGFR) beta.
22
Q
What are the main adverse effects of toceranib
A
- Gastrointestinal toxicosis,
- myelotoxicosis,
- musculoskeletal disorders,
- depigmentation
- hypertension
- hypothyroidism
23
Q
Which tumors respond to the direct action of Toceranib
A
Mast cell tumors (MCTs) and gastrointestinal stromal tumors (GISTs).
24
Q
What is the prevalence range of c-KIT mutations in canine MCTs
A
8-45%
25
Which tumor types respond better to Toceranib's indirect actions
Epithelial malignancies
26
What are the two classifications of chemotherapy drugs regarding extravasation potential
"Irritants" and "Vesicants"
27
List four immediate management steps for any extravasation event
1) Stop drug administration immediately,
2) Apply gentle negative pressure to remove drug,
3) Remove the catheter gently,
4) Avoid occlusive bandaging
28
Name examples of irritant chemotherapy drugs.
Platinum drugs (carboplatin, cisplatin),
dacarbazine,
mitoxantrone,
29
What are the typical effects of irritant drug extravasation
Mild to moderate erythema, edema, and crusting causing discomfort
30
Name examples of mild vesicant chemotherapy drugs
Vinca alkaloids (vincristine, vinblastine, vinorelbine)
31
What compresses should be applied for mild vesicant extravasation?
Warm compresses for 15-20 minutes, every 6 hours, for 2-3 days
32
Name three examples of serious vesicant chemotherapy drugs
Anthracyclines (doxorubicin, epirubicin),
dactinomycin,
mechlorethamine
33
What compresses should be applied for serious vesicant extravasation?
Cold compresses for 15-20 minutes, every 6 hours, for 2-3 days (opposite to mild vesicants)
34
What specific antidote can be used for doxorubicin extravasation, and when must it be administered?
IV dexrazoxane (10× the doxorubicin dose) within 3 hours, repeated at 24 and 48 hours.
35
When do neutrophil nadirs typically occur post-chemotherapy treatment
5-10 days post-treatment
36
When do platelet nadirs typically occur post-chemotherapy treatment
7-14 days post-treatment
37
Which genetic mutation increases risk of chemotherapy-induced myelosuppression in certain breeds?
Mutations in the ABCB1-1delta (MDR-1) gene
Collies, Australian Shepherds, and related breeds
38
Which chemotherapy agents commonly cause myelosupression
Cyclophosphamide, carboplatin, CCNU, Vincristin, Vinorelbine, Doxorubicin, mitoxantrone
39
Which class of agents may cause cumulative and irreversible thrombocytopenia with chronic use
Alkylating agents (CCNU, chlorambucil, melphalan).
40
Which dog breeds are most susceptible to chemotherapy-induced alopecia
Continuously-growing hair breeds: Maltese, Bichon Frisé, Poodles, certain Terrier breeds, Shih-Tzu, and Old English Sheepdog.
41
What chemotherapeutic agent causes focal dermatologic reaction in approximately 50% of dogs
RAB
42
What is the syndrome characterized by erythema, ulceration and alopecia that can occur with liposomal doxorubicin
Palmar-plantar erythrodysesthesia ("hand-foot syndrome")
43
What vitamin can reduce the severity of liposomal doxorubicin skin lesions in dogs
Pyridoxine (vitamin B6)
44
How does chemotherapy induce vomiting via the chemoreceptor trigger zone (CTZ)
Via neurotransmitters such as serotonin and substance P binding to 5-HT3 and neurokinin 1 (NK1) receptors.
45
What is the mechanism of action of crofelemer in treating chemotherapy-induced diarrhea?
It inhibits secretion of chloride ions and water by GI epithelial cells.
46
Which chemotherapy drug is primarily associated with cardiac toxicosis?
Doxorubicin
47
At what cumulative dose does the risk of doxorubicin cardiac toxicity significantly increase?
>180 mg/m²
48
What agent can be co-administered to reduce the risk of doxorubicin cardiotoxicity
Dexrazoxane (an iron chelator).
49
Which chemotherapy drug is notably hepatotoxic in dogs, causing increased ALT in up to 86% of treated animals?
Lomustine (CCNU)
50
What is the nature of CCNU-induced liver damage?
Cumulative and often irreversible damage,
with acute liver failure rarely occurring after a single treatment
51
Name two hepatoprotectants that may reduce the severity of chemotherapy-induced liver damage
S-adenosylmethionine and silybin
52
Which chemotherapy drugs require dose adjustments with pre-existing liver disease due to biliary excretion
Vinca alkaloids and doxorubicin
53
What neurologic effect can vincristine cause
Ileus due to neurotoxic effect on enteric motor function
54
Why is 5-fluorouracil contraindicated in cats
It can be neurotoxic and is fatal to cats
55
Which chemotherapy drugs are known nephrotoxicants
Cisplatin (dogs),
ifosfamide (dogs & cats),
streptozotocin (dogs)
56
Which chemotherapy drugs can cause Sterile Hemorrhagic Cystitis (SHC)
Cyclophosphamide and ifosfamide
57
What metabolite causes direct bladder irritation leading to SHC
Acrolein, an inactive metabolite
58
What drug is administered concurrently with high-dose cyclophosphamide to reduce the risk of SHC
Furosemide
59
Why is cisplatin contraindicated in cats
It causes fatal pulmonary edema when administered IV to cats
60
Which drug has been associated with diabetes in approximately 40% of cases
Streptozotocin (toxic to pancreatic beta cells)
Used for treatment of insulinoma
61
What unusual side effects have been associated with toceranib phosphate
Pancreatitis and lameness
62
Which drugs have been associated with pulmonary fibrosis
Bleomycin, high-dose CCNU in cats, and RAB
63
Which chemotherapy drug can cause true IgE-mediated hypersensitivity reaction
L-asparaginase
64
What measures can reduce the risk of hypersensitivity reactions with L-asparaginase
Administer SC or IM instead of IV, or premedicate with diphenhydramine
65
What causes anaphylactoid reactions with rapid IV administration of doxorubicin
Histamine release from mast cells (not true IgE-mediated hypersensitivity)
66
Melphalan
* Alkylating agent (Nitrogen mustard)
* DNA cross linking
* Myelosupression
67
Cyclophosphamide
* Alkylating agent (Nitrogen mustard)
* DNA cross-linking (prodrug)
* Neutropenia, **sterile haemorrhagic cystitis**
68
Ifosfamide
* Alkylating agent (Nitrogen mustard)
* DNA cross-linking (prodrug)
* **nephrotoxicity**, myelosuppression, **sterile haemorrhagic cystitis**
69
Chlorambucil
* Alkylating agent (Nitrogen mustard)
* DNA alkylation
* Myelosupression
70
Lomustine (CCNU)
* Alkylating agent (nitrosoureas)
* DNA Alkylation
* Myelosuppression, **cumulative hepatotoxicity**
71
Streptozotocin
* Alkylating agent (nitrosoureas)
* DNA alkylation
* GI toxicity and myelosupression, **beta cell toxicity**
72
Dacarbazine
* Alkylating agent
* DNA methylation
* Gi toxicity, myelosuppression
73
Procarbazine
* Alkylating agent
* DNA methylation
* Gi toxicity and myelosuppression
74
Mechlorethamine
* Alkylating agent (Nitrogen mustard)
* DNA cross linking
* **Vesicant**, myelosuppression, GI toxicity
75
Doxorubicin
* Antitumour antibiotic
* DNA intercalation, topoisomerase II inhibition
* **Cumulative cardiotoxicity, vesicant**, myelosuppression, GI toxicity
76
Mitoxantrone
* Antitumour antibiotic
* DNA intercalation, topoisomerase II inhibition
* myelosuppression
77
Actinomycin D
* Antitumour antibiotic
* DNA intercalation, RNA/protein synthesis inhibition
* Vesicant, GI toxicity and myelosuppression
78
Cytosine Arabinoside
* Antimetabolite
* DNA polymerase inhibition
* Myelosuppression, GI toxicity
79
Methotrexate
* Antimetabolite
* Dihydrofolate reductase inhibition
* Myelosuppression, GI toxicity
80
Gemcitibine
* Antimetabolite
* Nucleoside analogue, inhibits DNA synthesis
* Myelosuppression
81
5-Fluorouracil
* Antimetabolite
* Uracil analogue, Thymidylate synthetase inhibition, inhibits DNA synthesis
* Myelosupression, GI toxicity
* **Contraindicated in cats **
82
Rabacfosadine
* Antimetabolite
* Nucleotide analogue
* GI toxicity, **idiosyncratic pulmonary fibrosis, dermatologic**
83
Paclitaxel
* Antimicrotubule agent (taxane)
* Causes abnormal organization of spindle microtubules and mitotic arrest
* **Hypersensitivity reactions**, myelosuppression
84
Vincristine, vinblastine, vinorelbine
* Antimicrotubule agent (vinca alkaloid)
* Microtubule assembly inhibition - metaphase arrest
* Vincristine - Peripheral neurotoxicity, GI ileus, vesicant
* Myelosupression, vesicant
85
Carboplatin and Cisplatin
* Platinum agents
* DNA cross linking
* Carboplatin - myelosuppression
* Cisplatin - **nephrotoxicity**, GI toxicity, **contraindicated in cats**
86
Hydroxyurea
* Ribonucleotide reductase inhibition, depletion of deoxyribonucleotide
* myeleosupression, onycholysis
87
L-asparaginase
* Asparagine depletion and inhibition of protein synthesis
* Hypersensitivity reactions
88
Toceranib, masitinib, imatinib
* Tyrosine kinase inhibitors
* RTK inhibition (KIT, VEGFR2, PDGFR)
* GI toxicity, hyporexia, proteinuria/PLN, hypertension, hepatotoxicity
89
Which chemotherapeutics target the S phase
Antimetabolites,
alkylating agents,
cross-linking agents,
topoisomerase inhibitors
90
Which chemotherapeutics target the M phase
Antimicrotubule agents
91
Which tumor type is most commonly associated with gastrointestinal ulceration
What is the mechanism
* Mast cell tumours
* Hyperhistaminemia stimulating gastric acid secretion
92
Which cytokines mediate cancer cachexia?
TNF-α, IL-1, and IL-6
93
Which canine tumors are commonly associated with hypercalcemia of malignancy?
T-cell lymphoma and anal sac apocrine gland adenocarcinoma
94
Which feline tumors are associated with hypercalcemia of malignancy?
Lymphoma, squamous cell carcinoma (SCC), and multiple myeloma
95
What are three tumor types associated with hypoglycemia?
What molecule typically mediates this
Insulinoma, hepatocellular tumors, and smooth muscle tumors
IGF-2
96
Which tumor is most commonly associated with hyperestrogenism?
What are the clinical sigs
* Sertoli cell tumors (especially in cryptorchid testes)
* Feminisation and BM toxicity
97
How common is anemia in dogs/cats with lymphoma?
Very common, reported in 30-58% of cases
98
How common is thrombocytopenia in dogs with cancer before treatment?
Present in 13-36% of dogs
99
Which neoplasm is associated with hyperglobulinemia?
Multiple myeloma
100
Which tumor types are associated with erythrocytosis
Renal tumors
101
What tumor is associated with nodular dermatofibrosis, and in which breed?
Renal cystadenocarcinomas, mostly in German shepherds
102
What type of tumor is associated with superficial necrolytic dermatitis?
Glucagon-secreting tumors
103
What tumor types are associated with feline paraneoplastic alopecia?
Pancreatic and biliary carcinomas
104
What tumor is associated with exfoliative dermatitis in cats?
Thymoma
105
Which tumor is most commonly associated with myasthenia gravis?
Thymoma
106
Which tumor types are associated with hypertrophic osteopathy?
Primary or metastatic lung tumors
107
What is the most common histopathological diagnosis in dogs with lymphoma
Diffuse large B cell lymphoma (DLBCL) - 50% cases
108
Which subclassification of lymphoma is most liekly to cause paraneoplastic hypercalcemia
T cell
109
Which dogs show a higher breed prevalacance for B cell lymphoma
Basset Hound, Cocker Spaniel, Border Collie, Doberman Pinscher
110
Which dogs show a higher breed prevalacance for T cell lymphoma
Boxer, Shih Tzu, Cavalier King Charles Spaniel, Airedale
111
Which breed are over represented in Indolent T-zone Lymphoma (TZL)
Golden retreiver ~40% cases
112
What proportion of dogs with Indolent T zone lymphoma (TZL) have a concurrent blood lymphcytosis
50%
113
Which anatomical location for lymphoma is more likely to have an associated paraneoplastic hypercalcemia?
Mediastinal
114
What is the WHO staging for lymphoma
* Stage I: Single lymph node
* Stage II: Multiple lymph nodes in a regional area (same side of diaphragm)
* Stage III: Generalized lymphadenopathy
* Stage IV: Liver and/or spleen involvement (± lymph node involvement)
* Stage V: Any other anatomic site, including bone marrow and blood
* Substage a: Without clinical signs of disease
* Substage b: With clinical signs of disease
115
What are the cluster of differentiation T cell markers?
CD3, CD5, CD4, CD8
116
What are the cluster of differentiation B cell markers?
CD20, CD21, CD79a
117
What is the pan-leucocyte marker
CD45
118
What is the leucocyte pre-cursor marker (immature lymphoid/myeloid cells)
CD34
119
Expression of MHCII is typically high or low in peripheral T cell lymphoma in dogs
Low
120
FeLV is strongly associated with which neoplastic diseases
Large cell lymphoma (usually T cell) and Leukaemia
121
FIV infected cats are more likely to develop which type of lymphoma
approx 5x more likely to develop lymphoma
typically B cell in extranodal sites
122
FeLV associated lymphoma is most likely foudn in which anatomical locations
Mediastinal lymphoma most common, followed by multicentric, spinal, renal, or ocular
GI and nasal not usually FeLV associated
123
What anatomical location is most common in cats and what are the 3 types
Gatrointestinal
* Mucosal T cell lymphoma (EATCL Type II): small/intermediate lymphocytes in LP
* Transmural T cell lymphoma (EATCL Type I): large granular lymphocytes
* Diffuse large B cell lymphoma (DLBCL)
124
What are some prognostic indicators for cats with lymphoma
* Response to treatment
* FeLV positivity - strong negative factor
* Large granular lymphoma - aggressive variant
125
What are some prognostic indicators for dogs with lymphoma
* Immunophenotype: T-cell (except TZL) worse than B-cell
* Clinical substage: b worse than a
* Hypercalcemia: negative factor
* GI involvement: negative factor
126
What are the CD features of most chronic lymphocytic leukemias (CLL) in dogs?
* At least 75% are CD8+ CD45+ T-cell in origin
* CD21+ B-cell CLL is the next most common subtype
127
What are the CD features of most chronic lymphocytic leukemias (CLL) in cats?
* Almost all cases are CD4+ cell in origin
128
Is CLL in cats associated with FeLV/FIV?
No
129
What characterises acute lymphoblastic leukemia (ALL)
* proliferation of immature lymphoblasts in BM
* Diagnosis based on >20% blasts in peripheral blood or BM
130
What CD marker typically distinguishes acute leukemia from lymphoma?
What proportion of dogs with ALL are negative for this marker?
CD34+
25% dogs with ALL are CD34-
131
Is ALL in cats associated with FeLV or FIV
FeLV
132
What characterises Myelodysplastic syndrome?
* Cytopenias in multiple cell lines
* Bone marrow usually normocellular to hypercellular with dysplastic changes
* Increased blasts but <20% of nucleated cells
133
What characterises multiple myeloma
Arises from single clone of plasma cells producing excess immunoglobulin (can be whole Ig moelcule or molecular portion)
134
What are some of the characteristic clinical findings with multiple myeloma
* Other cytopenias (anaemia, thrombocytopenia and sometimes neutropenia)
* Bone lesion with dicrete osteolytic painful areas (vertebrae, ribs, pelvis, long bones)
* Coagulation and bleeding disorders
* Excess light chains (bence jones proteins) can cause renal damage
135
What are the diagnostic criteria for multiple myeloma
Need>/=2
* BM plasmacytosis (>20%)
* Serum monoclonal gammopathy
* Osteolytic lesions
* Bence-Jones proteinuria
136
What is BRAF
a gene and associated protein that helps control cell growth
137
What is the BRAF mutation and what disease can it help identify
* Specific mutation detected is called BRAF V595E
* More than 80% of dogs with transitional cell carcinoma (TCC) have this BRAF V595E mutation
138
What is the sensitivity and specificity of BRAF
Testing has >85% sensitivity with 100% specificity when used on free-catch urine samples
