History and Types of Cancer Chemotherapy

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Questions and Answers

What is the primary mechanism of action for folate antagonists in cancer treatment?

Stimulation of DNA repair mechanisms

Inhibition of dihydrofolate reductase (correct)

Inhibition of RNA polymerase

Activation of purine synthesis

Which nucleotide analog is known for having a greater affinity for dihydrofolate reductase compared to folate?

Fluorouracil

Methotrexate (correct)

Cytarabine

Azacitidine

What effect do purine and pyrimidine antagonists have on DNA?

They enhance proper base pairing

They lead to permanent DNA modifications (correct)

They stimulate DNA synthesis

They prevent RNA transcriptions

What is one potential side effect associated with anthracycline antibiotics?

Cardiac toxicity Signup and view all the answers

During which phase of the cell cycle do most anticancer effects of anthracyclines occur?

S phase Signup and view all the answers

Which two main groups are classified as antibiotic anti-tumor drugs?

Anthracyclines and bleomycins Signup and view all the answers

What is a common treatment complication associated with the use of methotrexate?

Liver toxicity Signup and view all the answers

What is the effect of folate antagonists on the synthesis of purines and pyrimidines?

They inhibit the synthesis Signup and view all the answers

What is the primary function of VEGF in the context of tumors?

To create new blood vessels for tumors Signup and view all the answers

Which class of drug is used to block the HER2 receptor in certain tumors?

Trastuzumab Signup and view all the answers

What is a common side effect associated with antineoplastic antibodies?

Immune reactions Signup and view all the answers

What is a noted concern regarding the use of thalidomide for treating blood cancers?

Possibility of birth defects Signup and view all the answers

What role do analogues of GnRH play in cancer treatment?

They affect hormone levels related to some cancers Signup and view all the answers

What is the primary function of alkylating agents in cancer chemotherapy?

Prevent DNA from unravelling for replication Signup and view all the answers

Which group of drugs is known for impairing the assembly of nucleic acids in cancer chemotherapy?

Antimetabolites Signup and view all the answers

In terms of their mechanism of action, alkylating agents are classified as cell cycle-specific or what?

Cell cycle non-specific Signup and view all the answers

Which of the following is an example of a nitrogen mustard used in chemotherapy?

Chlorambucil Signup and view all the answers

What is the role of folate antagonists in cancer treatment?

Inhibit the synthesis of DNA by blocking folic acid Signup and view all the answers

Which of the following is considered a characteristic of cytotoxic agents?

Inhibit cell replication Signup and view all the answers

Which type of chemotherapy includes drugs that comprise alkyl groups and react chemically with DNA?

Alkylating agents Signup and view all the answers

What distinguishes cell cycle specific agents from cell cycle non-specific ones?

Ability to only affect replicating cells Signup and view all the answers

What is a significant characteristic of the mitotic inhibitors?

They lead to disruption of spindle formation. Signup and view all the answers

Which of the following is true regarding vinca alkaloids?

They are derived from plants and have neurotoxic effects. Signup and view all the answers

What is a common use for podophyllins?

Effective in treating leukaemias and lymphomas. Signup and view all the answers

What defines the action of taxanes in cancer treatment?

They stimulate the immune response. Signup and view all the answers

How do bleomycin and mitomycin exert their anti-tumor effects?

By blocking thymidine incorporation into DNA. Signup and view all the answers

Which of the following phases do mitotic inhibitors specifically target?

M phase. Signup and view all the answers

What is a critical precaution when administering vinca alkaloids?

They should never be given intrathecally. Signup and view all the answers

What effect do mitotic inhibitors have on mitosis?

They 'freeze' mitosis in the metaphase stage. Signup and view all the answers

Study Notes

History of Cancer Chemotherapy

1940s: Nitrogen mustards (chemical warfare agents) were discovered, Goodman & Gilman were pioneers
1948: Folic acid antagonists (antimetabolites) were introduced
1950s: 6-MP (6-mercaptopurine) and Vinca alkaloids were discovered
1965: Combination therapy was introduced

Types of Cancer Chemotherapies

Radiopharmaceuticals: Also known as "nuclear medicine" or "radiation oncology"
Anti-neoplastic agents: These are drugs that act against cancer cells
- Cytotoxic agents:
  - Alkylating agents
  - Antimetabolites
  - Antitumour antibiotic agents
  - Mitotic inhibitors
- Hormonal chemotherapy / Miscellaneous

Cytotoxic agents

May have different sites of action on cell division cycle
ALL inhibit cell replication (anti-proliferative)
Classified as cell cycle specific OR cell cycle non-specific
Classification is important for drug choice

Alkylating agents

Contain alkyl groups (methyl –CH3, ethyl –CH2CH3)
React with DNA to form strong bonds
Hold DNA strands together (like a zipper stuck)
Prevent DNA from unravelling for DNA replication or RNA transcription
Slow or stop the cell cycle - Mainly at the S phase

Antimetabolites

Analogues of folic acid OR purine/pyrimidine bases
Inhibit enzymes involved in pathways of macromolecular synthesis
Act as false "building blocks", causing impaired polymers of nucleic acids to be assembled
3 main groups:
- Folate antagonists (e.g., methotrexate (pro-drug))
- Purine antagonists (e.g., mercaptopurine)
- Pyrimidine antagonists (e.g., fluorouracil)

Antimetabolites: Folate antagonists

Folate (vitamin B9) is essential for production of DNA and RNA
Children with leukemia had worse outcomes when taking folic acid
Folate antagonists mainly act by inhibiting the enzyme dihydrofolate reductase

Antimetabolites: Purine & Pyrimidine antagonists

Can be incorporated into DNA strands replacing the correct base
Form permanently modified DNA
Cause improper base pairing -> improper transcription to RNA
May also act as inhibitors on enzymes of DNA synthesis
Phase specific - Act particularly at the S phase of the cell cycle

Antibiotic anti-tumour drugs

2 main groups:
- Anthracyclines
- Bleomycins
Called antibiotics because compounds are isolated from one living organism (fungi) and act against another living organism (neoplastic cell)

Antibiotic anti-tumour drugs: Anthracyclines

1950s - Attempts to isolate anti-cancer compounds from microbes in soil (e.g., daunorubicin, doxorubicin, idarubicin)
Multiple modes of action (MOA), not fully understood
Bind directly to DNA, inhibiting DNA and RNA synthesis
Inhibit topoisomerase II
Intercalate with DNA to impair DNA transcription
Cell-cycle specific - S phase
Cardiac toxicity, lifetime maximum dose

Antibiotic anti-tumour drugs: Bleomycins

e.g., bleomycin, mitomycin (from Streptomyces species)
Block incorporation of thymidine into DNA, also degrade DNA that is already formed
Cell-cycle non-specific - G2, M, G0

Mitotic inhibitors

Natural products - from plants
3 groups:
- Vinca alkaloids
- Podophyllotoxins
- Taxanes
Main action at the metaphase stage of mitotic division

Mitotic inhibitors: Vinca alkaloids

From Vinca (Europe, Africa, Asia) "periwinkle"
e.g., vincristine, vinorelbine (oral), vinflunine, vinblastine
Relatively non-toxic compared to other cytotoxic agents
Exceptionally neurotoxic - Special precautions to not give intrathecally

Mitotic inhibitors: Podophyllins

Originally isolated from rhizomes of May Apple
e.g., etoposide, teniposide
Kill cells in the S and G2 phase in addition to the M phase
Used in leukaemias and lymphomas

Mitotic inhibitors: Taxanes

From Taxus (yews)
e.g., paclitaxel, docetaxel
Also stimulate the immune response
Used to treat breast, lung, and ovarian cancer

Hormonal treatment

Treatment of neoplasia that are sensitive to hormonal growth controls
e.g., for thyroid, breast, and prostate cancers
Includes: corticosteroids, androgens/anti-androgens, oestrogens/anti-oestrogens, progestogens, analogues of gonadotrophin releasing hormone (GnRH)

Miscellaneous Treatments

Antineoplastic antibodies
- Bind to a specific antigen or factor needed by a cancer cell to proliferate
VEGF (Vascular Endothelial Growth Factor)
- Needed to create new blood vessels for tumours
- Blocked by bevacizumab (Avastin)
EGFR (Epidermal growth factor receptor)
- Needed for new ‘endothelial cells’
- SCC, head and neck, colorectal
- Cetuximab (Erbitux)
HER2 (human epidermal growth factor receptor 2)
- Overexpression in some tumours, such as breast and gastric
- Blocked by Trastuzumab (Herceptin)
Thalidomide (and derivatives)
- Used for blood cancers (leukaemia, lymphoma, and multiple myeloma)
- Unknown mechanism of action, likely immunosuppressive and anti-angiogenesis
- BIRTH DEFECTS! Pregnancy Category X

Problems associated with cancer chemotherapy

Immune reactions
Increasing individual drug resistance
Cost

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Description

Explore the evolution of cancer chemotherapy from the 1940s to modern practices. This quiz covers key developments, types of therapies, and classifications of cytotoxic agents. Test your knowledge on historical milestones and therapeutic strategies in combating cancer.