Neoplasia/Hematology - Pharmacology - Chemotherapy; Targeted Therapy; Cancer Immunology Flashcards by Jason Worley

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

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Name a few examples of alkylating agents:

BCN

CPA

Busulfan, cyclosphosphamide, nitrosoureas (carmustine and lomustine);

cisplatin, procarbazine, allopurinol

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What type of chemotherapeutic agent is the following?

Busulfan

Alkylating agent

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What type of chemotherapeutic agent is the following?

Cyclosphosphamide

Alkylating agent

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What type of chemotherapeutic agent is the following?

Nitrosoureas (carmustine and lomustine)

Alkylating agents

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What type of chemotherapeutic agent is the following?

Cisplatin

Alkylating agent

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What type of chemotherapeutic agent is the following?

Procarbazine

Alkylating agent

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What type of chemotherapeutic agent is the following?

Allopurinol

Alkylating agent

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What is the major toxic side effect of the chemotherapeutic agent cyclophosphamide?

Hemorrhagic cystitis

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What are the major toxic side effects of the chemotherapeutic agents procarbazine, cisplatin, and carboplatin?

Nephro- and ototoxicity

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What are the major toxic side effects of alkylating agents in general?

Bone marrow depression

(leukopenia / thrombocytopenia)

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What type of chemotherapeutic agent is the following?

Methotrexate

Anti-folate

(anti-metabolite)

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What type of chemotherapeutic agents are the following?

5-fluorouracil

Cytarabine

Anti-pyrimidines

(anti-metabolites)

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What type of chemotherapeutic agents are the following?

6-mercaptopurine

6-thioguanine

Anti-purines

(anti-metabolites)

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What enzyme does methotrexate inhibit in its role as a chemotherapeutic agent?

Dihydrofolate reductase

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What enzyme does 5-fluorouracil inhibit in its role as a chemotherapeutic agent?

Thymidylate synthase

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What can be administered to reverse the inhibition of dihydrofolate reductase caused by methotrexate?

Leucovorin

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What enzyme activates 6-thioguanine and 6-mercaptopurine?

HGPRT

(to become purine analogs)

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How does cytarabine affect normal cellular function?

Its incorporation into DNA induces apoptosis

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True/False.

Cytarabine is basically a purine analog.

False.

Cytarabine is basically a pyrimidine analog.

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True/False.

The triphosphate form of cytarabine is the active form.

True.

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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.

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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.

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Describe the mechanism of action of taxanes (e.g. paclitaxel and docetaxel) as chemotherapeutic agents.

Microtubule stabilization

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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 **_hematolymphat_**ic 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 **neo****adjuvant**therapy 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: 1. Does it \_\_\_\_\_\_\_\_\_ 2. Is it \_\_\_\_\_\_\_\_ 3. Is it \_\_\_\_\_\_\_\_ 4. Can it ________ in \_\_\_\_\_\_\_\_

# Fill in the blanks for the stages of drug testing: 1. Does it **_work?_** 2. Is it **_safe?_** 3. Is it **_better?_** 4. 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 cyto**_static_**.

**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 **_hyper_**activate in order to kill tumor cells.

What is the name for the PD-1 receptor?

**P**rogrammed cell **D**eath 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) **Atezoliz**umab (PD-L1) **Durval**umab (PD-L1)

**_Pembroliz_**umab (PD-1) **_Nivol_**umab (PD-1) **Atezoliz**umab (PD-L1) **Durval**umab (PD-L1)

Name a few examples of PD-1/PD-L1 inhibitors used in cancer therapy: **Pembroliz**umab (PD-1) **Nivol**umab (PD-1) \_\_\_\_\_\_\_umab (PD-L1) \_\_\_\_\_\_\_umab (PD-L1)

**Pembroliz**umab (PD-1) **Nivol**umab (PD-1) **_Atezoliz_**umab (PD-L1) **_Durval_**umab (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.

**Ipili**mumab

**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?

**C**himeric **a**ntigen **r**eceptor - 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 ***auto***graft 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?

**Tociliz**umab

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

Neoplasia/Hematology - Pharmacology - Chemotherapy; Targeted Therapy; Cancer Immunology Flashcards

(93 cards)