Pharmacology: Cancer and Chemotherapy

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Questions and Answers

Which phase of the cell cycle is most susceptible to cancer chemotherapy?

M phase

S phase (correct)

G1 phase

G2 phase

What is the primary goal of ideal cancer chemotherapy?

Kill all immune cells

Kill all dormant cells

Kill all cancer cells (correct)

Kill all growing cells

What is the mechanism of multidrug resistance (MDR) in cancer cells?

Mutations in deactivating enzymes

Increased drug uptake

Increased drug inactivation

p-glycoprotein effluxes the drug (correct)

Which type of cancer chemotherapy agent is self-limiting?

Antimetabolites Signup and view all the answers

What is an important consideration in choosing a cancer chemotherapy drug?

Tumor type and location Signup and view all the answers

What is the purpose of intermittent high-dose therapy in cancer chemotherapy regimens?

To allow normal cells to recover Signup and view all the answers

What is a general consideration in cancer chemotherapy that affects the patient's ability to tolerate drugs and side effects?

All of the above Signup and view all the answers

What is the goal of combination chemotherapy?

To select drugs with different mechanisms of action and minimal overlapping toxicity Signup and view all the answers

What is a common feature of cancer cells?

Shift in control mechanisms for growth and differentiation Signup and view all the answers

What is the second leading cause of death in the US?

Cancer Signup and view all the answers

What type of cancer arises from epithelial cells?

Carcinomas Signup and view all the answers

What is the term for the proliferation of immature progenitors that circulate in the blood?

Leukemia Signup and view all the answers

What is the term for a type of cancer that occurs in the lymph system?

Lymphoma Signup and view all the answers

What is the term for cancer of connective or supportive tissue?

Sarcoma Signup and view all the answers

What is the goal of cancer chemotherapy?

To kill cancer cells Signup and view all the answers

What is the term for the ability of chemotherapeutic agents to selectively target cancer cells?

Selective toxicity Signup and view all the answers

What is the primary mechanism of action of alkylating agents in anti-cancer chemotherapy?

Alkylating DNA, resulting in cross-linking and DNA damage Signup and view all the answers

Which of the following anti-cancer chemotherapy agents is an example of an antimetabolite?

Methotrexate Signup and view all the answers

What is the mechanism of action of methotrexate in anti-cancer chemotherapy?

Inhibiting DNA synthesis by blocking the action of thymidylate synthetase Signup and view all the answers

Which of the following is a side effect of vincristine, a microtubule inhibitor?

Peripheral neuropathy Signup and view all the answers

What is the mechanism of action of topoisomerase II inhibitors, such as etoposide, in anti-cancer chemotherapy?

Inhibiting the relaxation of supercoiled DNA, leading to DNA breaks Signup and view all the answers

Which of the following is a mechanism of resistance to methotrexate, an antimetabolite?

Decreased uptake of the drug into the cell Signup and view all the answers

What is the primary mechanism of action of antibody-directed enzyme prodrug therapy (ADEPT)?

Delivering a toxin or drug directly to the tumor site Signup and view all the answers

Which of the following is a targeted therapy that inhibits the activity of the epidermal growth factor receptor (EGFR)?

Cetuximab Signup and view all the answers

What is the primary mechanism of action of the platinum-based anti-cancer chemotherapy agent, cisplatin?

Forming DNA adducts, leading to DNA damage and subsequent cell death Signup and view all the answers

Which of the following is a characteristic of targeted therapy, as compared to traditional anti-cancer chemotherapy?

Increased specificity for tumor cells, leading to fewer side effects Signup and view all the answers

Study Notes

Cancer (Neoplastic Disease)

Cancer is a group of diseases characterized by abnormal cell growth and a shift in control mechanisms for growth and differentiation.
Cancer cells infiltrate into organs and interfere with normal functioning.
There is no single cure for cancer.

Cancer Statistics

Second leading cause of death in the US (500,000 deaths per year).
Common cancer types in males: lung, prostate, colon and rectum.
Common cancer types in females: lung, breast, colon and rectum, and uterus.

Types of Cancers

Hematologic Malignancies: tumors of blood-forming organs and cells.
- Leukemias: proliferation of immature progenitors that circulate in blood.
  - Acute lymphocytic leukemia (ALL): proliferation of immature lymphoblasts in bone marrow.
  - Chronic lymphocytic leukemia (CLL): proliferation of immature B cells.
  - Acute myelocytic leukemia (AML): proliferation of immature myeloid cells in bone marrow.
  - Chronic myelocytic leukemia (CML): proliferation of myeloid cells; characterized by the Philadelphia chromosome.
- Lymphomas: tumors of the lymph system.
  - Hodgkin's Disease: cancer of lymph nodes.
  - Non-Hodgkin's lymphoma: cancer of lymphocytes.

Solid Tumors

Can occur in any organ or tissue; malignant (metastatic and invasive).
Carcinomas: arise from epithelial cells; malignant by definition.
- Examples: squamous cell carcinoma (arises from basal cells of skin); glandular epithelial cells of breast.
Sarcomas: cancer of connective or supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue.
- Examples: osteogenic sarcoma (arises from osteoblasts, chondroblasts, fibroblasts).

Cancer Chemotherapy

Goal: to be discussed.
Selective Toxicity: to be discussed.
Immune System: to be discussed.
Other aspects of cancer chemotherapy: to be discussed.### Hodgkin's Disease
Examples of Hodgkin's disease treatment: vincristine, methotrexate, 6-mercaptopurine, and prednisone (acute childhood lymphoblastic leukemia)

Adjuvant Therapy

Use of drugs in addition to surgery and radiation therapy to remove localized tumors and any remaining tumor cells
Cytotoxic chemotherapy (CCT) is used to eliminate remaining tumor cells and prevent metastasis

Drug Toxicity

CCT agents have a therapeutic index of 1, meaning the therapeutic dose is similar to the toxic dose
Cytotoxic agents kill all rapidly growing cells, including:
- Bone marrow cells, leading to leukopenia, thrombocytopenia, and anemia
- GI tract cells, leading to vomiting, diarrhea, and ulceration
- Hair follicles, leading to alopecia
- Tissues undergoing repair, leading to impaired wound healing
- Tumor cells, leading to hyperuricemia and kidney damage

Classes of Cancer Chemotherapeutic Agents

Inhibitors of DNA synthesis:
- Alkylating agents (e.g. nitrogen mustards, nitrosoureas, and methanesulfonate esters)
- Antifolates (e.g. methotrexate)
- Antibiotics (e.g. dactinomycin, doxorubicin, and bleomycin)
Antimetabolites:
- Purine analogs (e.g. 6-mercaptopurine, 6-thioguanine)
- Pyrimidine analogs (e.g. 5-fluorouracil, cytarabine)
Microtubule inhibitors:
- Vinca alkaloids (e.g. vincristine, vinblastine)
- Taxanes (e.g. paclitaxel, docetaxel)
Chromatin function inhibitors:
- Podophyllotoxins (e.g. etoposide, teniposide)
- Camptothecin

Alkylating Agents

Mechanism of action: form covalent bonds with nucleophilic groups in proteins and nucleic acids
Examples:
- Nitrogen mustards (e.g. cyclophosphamide, mechlorethamine, chlorambucil, and melphalan)
- Nitrosoureas (e.g. BCNU, CCNU, and methyl-CCNU)
- Methane sulfonate esters (e.g. busulfan)
- Triazenes (e.g. dicarbazine)
- Ethyleneimines (e.g. triethylenemelamine, triethylenethiophosphamide)

Folic Acid Analogs (Antifolates)

Mechanism of action: competitive inhibitors of dihydrofolic acid reductase (DHFR)
Examples:
- Methotrexate (MTX)
- Aminopterin
- Amethoperin

Antimetabolites

Interfere with nucleic acid biosynthesis
Examples:
- Purine analogs (e.g. 6-mercaptopurine, 6-thioguanine)
- Pyrimidine analogs (e.g. 5-fluorouracil, cytarabine)

Microtubule Inhibitors

Mechanism of action: bind to microtubules and inhibit their formation or stability
Examples:
- Vinca alkaloids (e.g. vincristine, vinblastine)
- Taxanes (e.g. paclitaxel, docetaxel)

Chromatin Function Inhibitors

Mechanism of action: inhibit topoisomerase I and II, leading to DNA strand breaks
Examples:
- Podophyllotoxins (e.g. etoposide, teniposide)
- Camptothecin

Immunotherapy

Monoclonal antibodies (e.g. rituximab, alemtuzumab, gemtuzumab)
Bispecific antibodies
Cancer vaccines

Targeted Therapy

Examples:
- Tyrosine kinase inhibitors (e.g. gefitinib, trastuzumab)
- mTOR inhibitors (e.g. temsirolimus)
- Proteasome inhibitors (e.g. bortezomib)

Traditional CCT vs. Targeted Therapy

Traditional CCT: non-specific, killing both cancer and normal cells
Targeted therapy: specific, targeting specific molecules or pathways involved in cancer development and growth

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Description

Learn about cancer as a neoplastic disease, its common features, and its impact on the human body. This quiz covers the basics of cancer and its treatment through chemotherapy.