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Principles of cancer chemotherapy

Treatment of cancer with an


antineoplastic drugs or a combination of drugs
into a standardised regimen

(1) Impair mitosis(cell division):


cytotoxic event or apoptosis
(2) Sites of action: DNA/metabolically active
tissues

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G1 phase: synthesis of cellular components of DNA synthesis
(growth phase)
S phase: replication of DNA/duplication of chromosomes
G2 phase: synthesis of enzymes/proteins
(prepared for mitosis)
M phase: mitosis(cell division)
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(3) Affects the proliferating normal &
abnormal cells

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Types of chemotherapy
(1) Combined modality chemotherapy
- combination of drugs & cancer treatments
- reduces the chances of resistance of a
particular drug
(2) Adjuvant therapy
- reduces the reactivation of cancer cells
- effective in killing fast dividing cancer cells
(3) Palliative chemotherapy
- reduces tumor load
- prolongs life

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Chemotherapeutic drugs

Affect cell division


or DNA synthesis

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Antimetabolites: 6-mercaptopurine

MOA

(1) Inhibition of purine


synthesis
(2) Produces non functional
RNA/DNA

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Alkylating agents: Mechlorathamine
MOA

Alkylation

Cross linkage b/t


guanine in DNA strands

DNA strands breakage

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Microtubules inhibitors
Vinca alkaloid Taxanes
Blocks mitosis in M phase Binds to tubulin

Binds to tubulin Increases polymerisation

Interferes the formation of


microtubules Stabilises the polymers

Dysfunction spindle Interphase arrest

Metaphase arrest
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Topoisomerase inhibitors

Epipodophyllotoxins Camptothecin
Blocks topoisomerase II S phase

Cleavage of enzyme-DNA Inhibits topoisomerase I


complex
Prevent religation of DNA
Irreversible DNA double breaks
strands break

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Alternative chemotherapeutic agents

Interferon
• suppress cell proliferation
• activates macrophage
• activates lymphocyte

Monoclonal antibodies
• reduces cancer cells proliferation
• E.g.: Rituximab, Transtuzumab

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Adjuvant therapy
(1) Radiation therapy
• Uses X rays
• Reduces the recurrence of cancer cells

(2) Targeted therapy


• Prevents abnormalities present in the cancer cells
• Targets specific proteins synthesis
• E.g.: breast cancer(inhibits action of HER2)

(3) Bone marrow transplantation

(4) Gene therapy


• DNA is used to replace altered genes: viral methods or non viral methods

(5) Immunotherapy
• Works out with body immune system

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Treatment regimens
Single drug therapy
- Treatment by a single type of drug

Multiple drugs therapy


- Combinations of several types of drugs with different mode
of actions/side effects
• more effective than single drug treatment
• Advantages: (i) provide maximal cell killing
(ii) effective against vast tumor population
(iii) delay drug resistance

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Adverse effects of cytotoxic drugs

(1)Immunosuppression
(2) Alopecia
(3) Nausea/vomiting
(4) Tetratogenicity
(5)erythema/xerostomia(rare)
(6)hyperuricemia

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