Pharmacology - Oncology 1 and 2

What are protooncogenes?

Normal genes that can be altered by carcinogens into oncogenes

What are oncogenes?

Genes that produce abnormal/excessive gene products disrupting normal cell growth

What is the most common tumor suppressor gene?

p53 gene

What does a steep dose-response curve imply in chemotherapy?

Both therapeutic effect and toxicity increase sharply with dose

Which drugs are cell cycle specific?

Antimetabolites, Bleomycin, Vinca alkaloids, Etoposide

What types of cancers are cell cycle specific drugs most effective against?

High growth fraction malignancies (e.g., leukemias)

Which drugs are cell cycle non-specific?

Alkylating agents, antibiotics, cisplatin, nitrosoureas

What are common general adverse effects of chemotherapy?

Hair loss, myelosuppression, nausea/vomiting, secondary cancers, extravasation

What is extravasation in chemo administration?

Leakage of vesicants into soft tissue causing damage

What are chemotherapy adjuncts used for?

To reduce or manage side effects of chemotherapy

What drug is used for chemotherapy-induced nausea/vomiting as a 5-HT antagonist?

Ondansetron

What drug blocks neurokinin-1 receptors for nausea?

Aprepitant

What is the mechanism of methotrexate?

Folic acid antagonist that inhibits dihydrofolate reductase (S-phase specific)

What is a major side effect of high-dose methotrexate?

Renal damage

What toxicity is associated with intrathecal methotrexate?

Neurotoxicity

What is 6-mercaptopurine used for?

Maintenance of remission in acute lymphoblastic leukemia

What is the mechanism of 5-fluorouracil (5-FU)?

Converted to 5FdUMP, inhibits thymidine synthesis → DNA inhibition

What resistance mechanism affects 5-FU?

Altered or increased thymidylate synthase

What is the target enzyme for both 5-FU and capecitabine?

Thymidylate synthase

What phase do antitumor antibiotics act in?

Non-specific (except Bleomycin), act directly on DNA

What is the MoA of anthracyclines?

Intercalate DNA and cause oxidative damage

How are anthracyclines administered?

IV only (inactivated by GI tract)

What is the dose-limiting side effect of anthracyclines?

Cardiotoxicity (CHF or cardiomyopathy)

What are two notable anthracycline side effects?

Red urine and visible veins due to red color

What is the MoA of Bleomycin?

Induces DNA strand breaks via oxidative process

What is the major toxicity of Bleomycin?

Pulmonary toxicity (Bleomycin lung → fibrosis)

What are alkylating agents most toxic to?

Rapidly dividing cells

What is a major concern with alkylating agents if cells survive?

Carcinogenic mutations

What is the dose-limiting side effect of alkylating agents?

Bone marrow suppression

What major AE is associated with cyclophosphamide?

Hemorrhagic cystitis → bladder fibrosis

What is vinca alkaloids MOA?

Binds tubulin → prevents mitotic spindle → mitotic arrest in metaphase

What is a unique side effect of vincristine?

Hyperuricemia (due to purine oxidation)

What is the MoA of taxanes like paclitaxel and docetaxel?

Stabilize microtubules in G2/M phase → prevent breakdown

What are dose-limiting and serious AEs of taxanes?

Neutropenia and hypersensitivity reactions

What is the MoA of steroid hormones in cancer therapy?

Agonists or antagonists to hormone receptors to inhibit tumor growth

What are common synthetic corticosteroids used in cancer?

Prednisone and dexamethasone

What are side effects of corticosteroids?

Hyperglycemia, fluid retention, HTN, immunosuppression, osteoporosis, ulcers

What is the MoA of tamoxifen?

SERM; blocks estrogen receptors in breast tissue

What is tamoxifen used for?

1st-line treatment of estrogen-sensitive breast cancer

What are major AEs of tamoxifen?

Hot flashes, vaginal discharge, thromboembolism

What is the MoA of anastrozole (aromatase inhibitor)?

Prevents conversion of androstenedione to estrogen

What is anastrozole used for?

Breast cancer

What is the MoA of leuprolide (GnRH analog)?

Occupies GnRH receptors → ↓ FSH and LH release

What is leuprolide used to treat?

Prostate and breast cancer

What are common side effects of leuprolide?

Hot flashes, impotence

What is flutamide's MoA?

Competes with testosterone for androgen receptors

What is flutamide used to treat?

Prostate cancer

What is a monoclonal antibody (MAB)?

Antibody from B lymphocytes against a single antigen type

What do all monoclonal antibody names end in?

-mab

What is a common AE of MABs?

Infusional hypotension

What is the MoA of cisplatin?

Acts like alkylating agent; inhibits DNA synthesis

What are cisplatin's main side effects?

Severe vomiting, nephrotoxicity, ototoxicity, neuropathy

Which cell cycle phases are most susceptible to cisplatin?

G1 and S phases

What is the MoA of topoisomerase I inhibitors?

Block TOP1 → DNA fragmentation during replication

What are major AEs of TOP1 inhibitors?

Myelosuppression (neutropenia), delayed diarrhea

What is the MoA of topoisomerase II inhibitors?

Inhibit TOP2 → causes DNA strand rupture

What is imatinib used to treat?

CML (chronic myeloid leukemia)

What are AEs of imatinib?

Edema, nausea, vomiting

What is erlotinib used to treat?

Non-small cell lung cancer

What is a common AE of erlotinib?

Diarrhea