Oncology Flashcards
What are the phases of the cell cycle?
Interphase - G0, G1, S, G2
M phase - mitosis and cytokinesis (w/in mitosis phase)
What happens in the G1 phase of the cell cycle
preparation for DNA replication- cell growth and protein synthesis
What happens in the S phase of the cell cycle?
DNA replication
What happens in the G2 phase of the cell cycle?
Condensation of genetic material
What are the four stages of mitosis?
Prophase
Metaphase
Anaphase
Telophase (and cytokinesis)
What are the three checkpoints in the cell cycle?
G1/S checkpoint
G2 checkpoint
M checkpoint
What happens at the G1/S checkpoint?
Decision point on whether to divide or enter G0
Checks for size, nutrients, molecular signals, DNA integrity
What happens at the G2 checkpoint?
Decision point on whether to pause in G2 and repair, or undergo apoptosis
Checks for DNA integrity and that DNA replication is complete
What happens at the M checkpoint?
Also known as spindle checkpoint
Makes sure all chromosomes are lined up in spindle and none are floating off in the cell
What checkpoints does p53 regulate?
G1 and G2
What activates p53 in normal cells?
DNA damage
Where in the cell cycle do antimetabolites work?
S phase
Where in the cell cycle do alkylating agents work?
Overall non-specific but do work in S phase
Where in the cell cycle do platinum agents work?
S phase
Where in the cell cycle do antitumor antibiotics work?
S and G2 phase
Where in the cell cycle do vinca alkaloids work?
M phase
Where in the cell cycle do taxanes work?
M phase
What is the MOA of antimetabolites?
Mimic normal purines and pyrimidines
This makes sense why they work in S phase (DNA replication)
What is the MOA of alkylating agents?
Cross-link DNA strands
This makes sense why they work in S phase (DNA replication)
What is the MOA of platinum agents?
Platinum compounds cross-link DNA strands –> Inhibits DNA synthesis
This makes sense why they work in S phase (DNA replication)
What is the MOA of antitumor antibiotics?
Inhibition of topoisomerase II –> obstruction of DNA and RNA synthesis
Multiple MOAs exist
What is the MOA of vinca alkaloids?
Mitotic spindle poisons; inhibit microtubule assembly
What is the MOA of taxanes?
Interfere with microtubule reorganization and disassembly
What are some examples of antimetabolite chemo drugs?
Methotrexante
5-FU
Azathioprine
Cytosine arabinoside (Cytosar)
Hydroxyurea
What are some exaples of alylators?
Cytoxan
Chlorambucil
Melphalan
Lomustine
What are examples of platinum agents?
Cisplatin
Carboplatin
What are examples of antitumor antibiotics?
Doxorubicn
Mitoxantrone
Bleomycin
What are examples of vinca alkaloids?
Vincristine
Vinblastine
Vinorelbine
What are examples of taxanes?
Paclitaxel
Docetaxel
What does the Gompertzian growth curve show?
Initial exponential phase of tumor growth occurs largely before tumor is clinically detectable AKA growth has slowed by the time we detect most tumors, which makes them less responsive to chemotherapy
Why are neutrophils most sensitive to chemotherapy?
They have shortest circulating lifespan of about 10 hours
What drug has a delayed double nadir?
Carboplatin
First nadir at 10-14d
Second nadir at 21d
What breeds of dogs are predisposed to alopecia with chemotherapy?
Anything with a continuously growing hair coat - poodles, Maltese, terriers, old English sheepdogs
What drugs cause indirect GI signs (nausea) via stimulation of the chemoreceptor trigger zone (CRTZ)?
Cisplatin
Streptozotocin
What is a unique side effect of vincristine?
Peripheral neuropathy (ileus, neuropathy)
What is the MOA of Cerenia (maropitant)?
Substance P inhibitor/Neurokinin-1 inhibitor (NK-1 is where substance P acts)
Central and peripherally acting
What is the MOA of Reglan/metoclopramide?
Centrally: dopamine (D2) antagonist, serotonin (5-HT3) antagonist in CRTZ
Peripherally: dopamine (D2) antagonist, serotonin (5-HT4) agonist
What is the MOA of Zofran/ondansetron?
Central and peripheral serotonin (5-HT3) antagonist
Is Flagyl/metronidazole bacteriostatic or bacteriocidal?
Bacteriocidal
What classes of chemotherapy drugs should you use with caution in MDR-1 mutants?
Vinca alkaloids
Antitumor antibiotics
Taxanes
What chemotherapy are the main vesicants?
Doxorubicin
Vincristine
How do you treat doxorubicin extravasation?
Stop infusion
Draw back to remove as much drug as possible
Ice pack the leg
Dexrazoxane/Zenecard
Do you heat pack or ice pack with vincristine?
Heat pack
Where are vinca alkaloids metabolized?
Liver - dose reduce based on tbili
What is a unique side effect of taxanes?
Hypersensitivity
What chemotherapy drugs have cumulative myelosuppression?
CCNU
Melphalan
Chlorambucil
What is the unique side effect of cytoxan?
Sterile hemorrhagic cystitis
Also nephrotoxicity
What metabolite is responsible for sterile hemorrhagic cystitis?
Acrolein
Fanconi syndrome was recently associated with what chemotherapy drug?
Chlorambucil
Reinert NC, Feldman DG. Acquired Fanconi syndrome in four cats treated with chlorambucil. J Feline Med Surg. 2016 Dec;18(12):1034-1040. doi: 10.1177/1098612X15593108. Epub 2015 Jul 13. PMID: 26170278.
What are the unique side effects of CCNU?
Hepatotoxicity
Pulmonary fibrosis (cumulative; rare in animals)
What drug must you ABSOLUTELY have a chemo hood for?
Mechlorethamine (Mustargen)
What tumor is streptozoticin sometimes used for?
Insulinoma
Where does streptozoticin concentrate and what might result from that?
Pancreatic Beta cells –> diabetes mellitus
What unique side effect is seen with cisplatin in cats?
FATAL pulmonary edema
Cisplatin splats cats
How is carboplatin excreted?
Renal excretion
Cisplatin has what unique side effect?
Nephrotoxicity
Also emetogenic
What unique side effect do we see with doxorubicin in dogs vs. cats?
Dogs - cumulative cardiotoxicity
Cats - cumulative nephrotoxicity
What tumor type should use avoid or take caution with using doxorubicin?
MCT - causes degranulation
Where is doxorubicin metabolized?
Liver - reduce if tbili is elevated
What is the MOA of Palladia?
Tyrosine kinase inhibitor –> blocks c-kit
Also works on VEGFR
What are potential side effects of Palladia?
Protein losing nephropathy
Systemic hypertension
Lameness/muscle cramping
GI side effects
What is the MOA of Tanovea (Rabacfosadine)?
It is a prodrug (GS-9219) of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine (PMEG) –> phosphorylated to PMEGpp which causes cytotoxicity due to inhibition of nuclear DNA polymerases
What are potential side effects of Palladia?
Dermatopathy
Pulmonary fibrosis
GI
BM suppression
Renal
Hepatic
What is the MOA of L-asparaginase?
Breaks down asparagine to starve cancerous lymphocytes
What is the major side effect of Elspar?
Allergic reaction
Rarely also pancreatitis
After how many doses does resistance to Elspar typically develop?
3-5 doses
What is Oncept and how does it work?
Bacterial plasmid melanoma vaccine
Contains human DNA encoding for tyrosinase inserted into a bacterial plasmid –> tyrosinase is the rate limiting enzyme in melanin production
What is the MOA of bisphosphonates?
Osteclast inhibition
What is potential toxicity of bisphosphonates?
Renal toxicity
Oral forms (aledronate): possible esophageal irritation/strictures +/- absorption issues
Which chemotherapy drugs can cross the BBB?
Antimetabolites - cytarabine, hydroxyurea
Alkylating agents - Lomustine, carmustine, procarbazine
What major CD markers are on B vs. T cells in flow cytometry?
B cells - CD21, MHC class II, CD79
T cells - CD3, CD4, CD8
What CD marker is found on all leukocytes?
CD45
Is PARR or flow more sensitive for minimal residual disease?
PARR (need as little as 1 lymphocyte in 100,000)
What is technically the gold standard for immunophenotyping in lymphoma?
IHC
What immunoglobulin is most commonly produced in multiple myeloma in dogs vs. cats?
Dogs: IgG or IgA
Cats: IgG
What are possible causes of renal disease in patients with multiple myeloma?
Bence Jones Proteinuria
Tumor infiltration into renal tissue
Hypercalcemia
Amyloidosis
Diminished perfusion secondary to HVS
Diagnosis of MM requires how many of the 4 criteria and what are they?
2 of 4
Monoclonal gammopathy
Lytic bone lesions
>20% plasma cells in bone marrow
Bence Jones proteinuria (25-40% of dogs have this)
Why can’t you determine Bence Jones proteinuria on a urine dipstick?
It’s the light chains of the Ig that are found in urine
What is the sensitivity and specificity of BRAF?
Sensitivity 85%
Specificity 99%
Myasthenia gravis is associated with what tumor type?
Thymoma (think myasthenia –> megaE)
Hypertrophic osteopathy can occur secondary to what?
Think respiratory things
Pneumonia
Lung tumors
Pulmonary mets
Also - Abdominal tumors
Ectopic ACTH secretion can occur (rarely) secondary to what?
Pulmonary lung tumors
Uncommon
Dermatologic paraneoplastic syndromes are associated with what tumor types?
Feline pancreatic carcinoma
Bile duct and HCC
Feline lymphoma
Renal caricnoma
Uterine leiomyoma
Thymomas
What proportion of hypercalcemic dogs have cancer?
2/3
What proportion of hypercalcemic cats have cancer?
1/3
What is the mechanism through which LSA/AGASACA/MM cause hypercalcemia?
Lymphoma and AGASACA - PTHrp
Multiple myeloma - lysis from bony lesions
What is the fluid of choice when rehydrating/diuresing a patient with hypercalcemia?
0.9% NaCl b/c it doesn’t contain calcium and is sodium heavy which forces renal tubules to flush out calcium
Are neoplastic or non-neoplastic causes more common in hypoglycemia?
Non-neoplastic
What tumor types are associated with paraneoplastic hypoglycemia?
Insulinoma
GI leiomyoma/sarcoma
HCC
Less common:
Renal adenocarcinoma
Lymphoma
Mammary carcinoma
What tumor types are associated with hyperviscosity syndrome?
Think in terms of mechanism:
Globulins: Multiple myeloma
Erythrocytes: Polycythemia vera
WBCs: CLL –> secondary due to monoclonal gammopathy