Neoplasia/Hematology - Pharmacology - Chemotherapy; Targeted Therapy; Cancer Immunology Flashcards
Describe the mechanism of action of chemotherapeutic alkylating agents:
binding ___ ________ positions in DNA;
causing strand _________;
________-________ing of DNA
Describe the mechanism of action of chemotherapeutic alkylating agents:
binding N7 guanosine positions in DNA;
causing strand breakage;
cross-linking of DNA
Name a few examples of alkylating agents:
BCN
CPA
Busulfan, cyclosphosphamide, nitrosoureas (carmustine and lomustine);
cisplatin, procarbazine, allopurinol
What type of chemotherapeutic agent is the following?
Busulfan
Alkylating agent
What type of chemotherapeutic agent is the following?
Cyclosphosphamide
Alkylating agent
What type of chemotherapeutic agent is the following?
Nitrosoureas (carmustine and lomustine)
Alkylating agents
What type of chemotherapeutic agent is the following?
Cisplatin
Alkylating agent
What type of chemotherapeutic agent is the following?
Procarbazine
Alkylating agent
What type of chemotherapeutic agent is the following?
Allopurinol
Alkylating agent
What is the major toxic side effect of the chemotherapeutic agent cyclophosphamide?
Hemorrhagic cystitis
What are the major toxic side effects of the chemotherapeutic agents procarbazine, cisplatin, and carboplatin?
Nephro- and ototoxicity
What are the major toxic side effects of alkylating agents in general?
Bone marrow depression
(leukopenia / thrombocytopenia)
What type of chemotherapeutic agent is the following?
Methotrexate
Anti-folate
(anti-metabolite)
What type of chemotherapeutic agents are the following?
5-fluorouracil
Cytarabine
Anti-pyrimidines
(anti-metabolites)
What type of chemotherapeutic agents are the following?
6-mercaptopurine
6-thioguanine
Anti-purines
(anti-metabolites)
What enzyme does methotrexate inhibit in its role as a chemotherapeutic agent?
Dihydrofolate reductase
What enzyme does 5-fluorouracil inhibit in its role as a chemotherapeutic agent?
Thymidylate synthase
What can be administered to reverse the inhibition of dihydrofolate reductase caused by methotrexate?
Leucovorin
What enzyme activates 6-thioguanine and 6-mercaptopurine?
HGPRT
(to become purine analogs)
How does cytarabine affect normal cellular function?
Its incorporation into DNA induces apoptosis
True/False.
Cytarabine is basically a purine analog.
False.
Cytarabine is basically a pyrimidine analog.
True/False.
The triphosphate form of cytarabine is the active form.
True.
Gemcitabine is a(n) ___-phase-specific anti-metabolite that enters cells via ______ and ______ transporters.
Gemcitabine is a(n) S-phase-specific anti-metabolite that enters cells via CNT and ENT transporters.
True/False.
Anti-metabolites have few negative side effects as chemotherapeutic agents.
False.
May cause hair loss, nausea, vomiting, myelosuppression, tumor lysis syndrome;
may cause neurologic, CV, GI, genitourinary, dermatologic, pulmonary, otic, ocular, and hepatobiliary toxicities;
may cause dysethesias, toxic epidermal necrolysis, and Stevens-Johnson syndrome;
etc.
Describe the mechanism of action of taxanes (e.g. paclitaxel and docetaxel) as chemotherapeutic agents.
Microtubule stabilization
Describe the mechanism of action of vinca alkaloids (e.g. vincristine and vinblastine) as chemotherapeutic agents.
Inhibition of microtubule formation
Describe the mechanism of action of anthracyclines and etoposides as chemotherapeutic agents.
Topoisomerase inhibition
Vinca alkaloids (e.g. vincristine, vinblastine) and taxanes (e.g. paclitaxel, docetaxel) mainly act at which phases of the cell cycle?
M phase
Name a few toxic side effects of paclitaxel.
Neutropenia, thrombocytopenia;
peripheral neuropathy
Name the main toxic side effect of vincristine.
Name the main toxic side effect of vinblastine.
Marrow depression;
peripheral neuritis
What is a common toxicity of vincristine and vinblastine (remember chemo man)?
Peripheral neuropathy (Chemo man’s V-shaped arms and legs)
What are two common toxicities of cisplatin (remember Chemo Man)?
Ototoxicity and kidney toxicity (both shaped like C’s on Chemo Man)
What is a common toxicity of bleomycin (remember Chemo Man)?
Pulmonary fibrosis (lungs look like B’s on Chemo Man)
What is a common toxicity of cyclophosphamide (remember Chemo Man)? How is it prevented?
Hemorrhagic cystitis (bicycle in half-pipe of Chemo Man); mesna
What is a common toxicity of adriamycin (doxorubicin) and daunorubicin (remember Chemo Man)?
irreversible, dose-dependent cardiotoxicity (heart failure)
Name a medication that blocks topoisomerase II.
Name two medications that block topoisomerase I.
Etoposide — (two supercoils at a time);
iratecan, topotecan — (one supercoil at a time)
Doxorubicin is an example of what type of chemotherapeutic agent?
An anthracycline
(a type of toposiomerase II inhibitor)
True/False.
Much of the cardiotoxicity caused by anthracyclines such as doxorubicin is due to oxidative reactions that damage DNA and mitochondrial membranes.
True.
Etoposide and teniposide are _________ alkaloids that block topoisomerase II and have a main toxic side effect of ______________ic toxicity.
Etoposide and teniposide are plant alkaloids that block topoisomerase II and have a main toxic side effect of hematolymphatic toxicity.
Bleomycin is an ____________ that can exert a chemotherapeutic effect by formation of _________ _________.
Bleomycin is an antibiotic that can exert a chemotherapeutic effect by formation of free radicals.
What is the main toxic effect of bleomycin?
Pulmonary fibrosis
Name two antibiotics commonly used as chemotherapeutic agents.
Bleomycin;
dactinomycin
___________ therapy encompasses all treatments that are administered before the primary cancer treatment, whereas ___________ therapy describes regimens administered after the primary treatment.
Neoadjuvant therapy encompasses all treatments that are administered before the primary cancer treatment, whereas adjuvant therapy describes regimens administered after the primary treatment.
Adjuvant therapy encompasses all treatments that are administered ________ the primary cancer treatment, whereas neoadjuvant therapy describes regimens administered ________ the primary treatment.
Adjuvant therapy encompasses all treatments that are administered after the primary cancer treatment, whereas neoadjuvanttherapy describes regimens administered before the primary treatment.
Which form of chemotherapy in addition to primary treatment has an increased likelihood of detecting micrometastases before they are clinically apparent?
(Adjuvant or neoadjuvant chemotherapy)
Neoadjuvant therapy
Which form of chemotherapy in addition to primary treatment has an decreased likelihood of resulting in overadministration of unnecessary treatment?
(Adjuvant or neoadjuvant chemotherapy)
Adjuvant chemotherapy
Fill in the blanks for the stages of drug testing:
- Does it _________
- Is it ________
- Is it ________
- Can it ________ in ________
Fill in the blanks for the stages of drug testing:
- Does it work?
- Is it safe?
- Is it better?
- Can it stay in market?
True/False.
Alkylating agents can lead to secondary leukemias.
True.
Tamoxifen can lead to what negative side effects?
Menopausal symptoms;
endometrial carcinoma;
thrombosis
Name two targeted therapies that specifically inhibit estrogen receptors at the breast.
Tamoxifen;
raloxifen
(also, tormifen)
True/False.
Tamoxifen and raloxifen are aromatase inhibitors that are largely cytotoxic.
False.
Tamoxifen and raloxifen are breast estrogen receptor inhibitors that are largely cytostatic.
True/False.
Although tamoxifen increases risk of thrombosis, it decreases the risk of damaging cardiovascular events.
True.
Name the medication most commonly used to modulate the estrogen receptor.
Name the medication most commonly used to modulate the HER-2/Neu receptor.
Tamoxifen;
trastuzumab
Name a few third-generation aromatase inhibitors.
Anastrozole;
letrozole;
exemestane
Name a steroidal antiestrogen medication that has a higher affinity for the estrogen receptor than tamoxifen.
Fulvestrant
Do progestins typically have strong antiestrogenic or antiandrogenic effects?
Both!
What medication is used for androgen antagonism at the level of the prostate?
Flutamide
(also bicalutamide, nilutamide)
Name the original medication synthesized to treat CML by blocking BCR-ABL tyrosine kinase.
Imatinib (Gleevec)
Name the main medication used to block the EGFR.
Gefitinib
(only effective in tumor cells with mutated or overexpressed EGFRs)
Name the mechanism of action of the following medications:
Palbociclib
Abemaciclib
Ribociclib
Cyclin D kinase 4/6 inhibition
_________ is a dual tyrosine kinase inhibitor that interrupts the HER-2/neu and epidermal growth factor receptor (EGFR) pathways.
Lapatinib is a dual tyrosine kinase inhibitor that interrupts the HER-2/neu and epidermal growth factor receptor (EGFR) pathways.
__________ is a nitrogen-containing bisphosphonate used to prevent bone loss and treat osteoporosis.
Pamidronate is a nitrogen-containing bisphosphonate used to prevent bone loss and treat osteoporosis.
Give an example of an mTor inhibitor sometimes used in cancer therapy.
Everolimus
Cancer therapies that block PARP have what effect on tumor cells?
Inability to correct DNA damage
Which BRCA mutation carries a higher risk of breast cancer development?
BRCA1 (55 - 65%)
What medication is often given prophylactically to prevent breast cancer development in high-risk women?
Tamoxifen
What medication is associated with DVT and endometrial carcinoma?
Tamoxifen
What medication type is better for post-menopausal women who need adjuvant or primary therapy for breast cancer?
Aromatase inhibitors
All women who have PR+ or ER+ breast cancer should be treated with anti-_________ therapy.
All women who have PR+ or ER+ breast cancer should be treated with anti-estrogen therapy.
What is the first line of natural defense against tumorigenesis?
DNA repair
What cell types provide some surveillance in watching out for cancer cells?
NK cells;
macrophages
What in particular do macrophages secrete upon finding a tumor cell?
TNF
Where are most natural killer cells in the body?
The bloodstream
Macrophages need to be ______activated in order to kill tumor cells.
Macrophages need to be hyperactivate in order to kill tumor cells.
What is the name for the PD-1 receptor?
Programmed cell Death protein 1
In normal, healthy tissues, PD-1 interaction with PD-L1 blocks what?
Autoimmunity
(downplays leukocyte activity)
Healthy tissues express what to inhibit leukocyte activity and prevent autoimmunity?
PD-L1
Many tumor cells up-regulate PD-___ to evade immune responses by binding PD-___ on leukocyte surfaces.
Many tumor cells up-regulate PD-L1 to evade immune responses by binding PD-1 on leukocyte surfaces.
Why do abnormal proteins expressed on tumor cell MHC (class I) not typically induce an immune response?
Lack of co-stimulation
(T cells that bind the MHCs without co-stimulation become anergic)
Name two receptors found on leukocytes that inhibit immune actiivty when bound,
PD-1
CTLA-4
Name a few of the ways that monoclonal antibodies can be used to modulate tumor cell activity:
Blocking _________ (e.g. trastuzumab);
inducing _________ (e.g. rituximab);
blocking _________ _________ proteins (e.g. nivolumab blocking PD-1);
conjugation of antibody to _________ or _________
Name a few of the ways that monoclonal antibodies can be used to modulate tumor cell activity:
Blocking receptors (e.g. trastuzumab);
inducing apoptosis (e.g. rituximab);
blocking immune regulatory proteins (e.g. nivolumab blocking PD-1);
conjugation of antibody to radioisotopes or toxins
Name a few examples of PD-1/PD-L1 inhibitors used in cancer therapy:
_______umab (PD-1)
_______umab (PD-1)
Atezolizumab (PD-L1)
Durvalumab (PD-L1)
Pembrolizumab (PD-1)
Nivolumab (PD-1)
Atezolizumab (PD-L1)
Durvalumab (PD-L1)
Name a few examples of PD-1/PD-L1 inhibitors used in cancer therapy:
Pembrolizumab (PD-1)
Nivolumab (PD-1)
_______umab (PD-L1)
_______umab (PD-L1)
Pembrolizumab (PD-1)
Nivolumab (PD-1)
Atezolizumab (PD-L1)
Durvalumab (PD-L1)
Name a few toxicities seen in up to ~20% of cases of PD-1/PD-L1 administration.
Pneumonitis;
colitis
(also endocrinopathy)
Name an example of a CTLA-4 inhibitor.
Ipilimumab
True/False.
Use of inhibitors of PD-1, PD-L1, or CTLA-4 in cancer therapy are all associated with inflammation of any organ system.
True.
What does the term ‘CAR-T cell’ stand for?
Chimeric antigen receptor - T cells
CAR-T cell therapy has been FDA approved for treatment of what disease(s)?
B-ALL;
diffuse large B cell lymphoma
(both must be CD19+)
True/False.
CAR-T cell therapy currently seems to be very effective, but it is also very expensive and associated with severe toxicities.
True.
(up to 80% response rates;
$750,000 per treatment;
cytopenias + neurotoxicities + cytokine release syndromes)
True/False.
CAR-T cell therapy is basically an allograft of T cells that have a high affinity for the specific tumor cells found in the patient (modified in the lab to have this high affinity).
False.
CAR-T cell therapy is basically an autograft of T cells that have a high affinity for the specific tumor cells found in the patient (modified in the lab to have this high affinity).
Cytokine release syndrome is a syndrome of massive inflammation mediated by IL-___ that leads to ______-like symptoms.
Cytokine release syndrome is a syndrome of massive inflammation mediated by IL-6 that leads to shock-like symptoms.
What monoclonal antibody is anti-IL-6 and can be used to treat cytokine release syndrome?
Tocilizumab
What are bispecific T cell engagers (BiTEs)?
A monoclonal antibody that connects T cells to tumor cells.
Give an example of a monoclonal antibody that acts as a bispecific T cell engager (BiTE).
Blinotumomab
