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Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies
23

Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Dec 26, 2015

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Lionel Stewart
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Page 1: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Cancer therapy - conventional

Surgery

Radiotherapy

Chemotherapy

Adjuvant therapies

Page 2: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Surgery

Advantages:

quick & effective;

largest no of cures;

confirmation of excision

Disadvantages:

no guarantee of complete removal;

critical normal tissues invasion

ineffective for metastasis.

Page 3: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Electromagnetic radiation

intranuclearXtranuclear

Page 4: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Radiotherapy

X-ray source

Page 5: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Radiotherapy sources

Page 6: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Biological effects

Rad is the unit of absorbed dose1 rad =100erg/g

Gy (Gray) 1 Gy = 100rads = joule/kg

Page 7: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Conformal radiotherapyAdvances in imaging techniquesE.g. Liver tumours

Time, Dose, Fractionation

Page 8: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Adjuvant radiotherapyBoron Neutron Capture Therapy

Page 9: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Adjuvant radiotherapyThermotherapy

MR-guided laser induced thermotherapy of osteiod osteoma

Page 10: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Adjuvant radiotherapyPhotodynamic therapy

Page 11: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Adjuvant radiotherapyBioreductive drug adjuvant therapy

Harmless prodrugUnder certain conditions is converted to a cytotoxic metabolite

E.g. AQ4N (alkylaminoanthraquinone N-oxide)

Harmless in oxic cellsConverted into cytotoxic AQ4 in hypoxic cells

combined with radiotherapy or chemotherapy

Page 12: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Chemotherapy

Works by affecting DNA synthesis and function

Page 13: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Classes of chemo agents

Methotrexate, 5-fluorouracil, cytosine arabinoside, 6-mercaptopurine

Analogues of normal metabolites

Function in 3 ways Substitution Competition for catalytic site Competition for regulatory site

1) Antimetabolites:

Page 14: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

antimetabolites serine hydroxymethyltransferase (SHMT)

thymidylate synthase (TS) dihydrofolate reductase (DHFR)

Page 15: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

methotrexate

choriocarcinoma

Folic acid antagonist

Dihydrofolate reductase

Reduced synthesis of A & G

Cytotoxicity reversed by leucovorin

Page 16: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Classes of chemo agents

Bacterial or fungal derivatives that affect cellular processes like DNA or protein synthesis

2) Antibiotics

Topoisomerase inhibitors

Page 17: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Doxorubicin (Adriamycin) Fungal anthracycline that has multiple effects 1) it intercalates within the DNA 2) causes single and double strand breaks and 3) inhibits topoisomerase II. Used against

leukaemias, breast, lung and ovarian cancer

Page 18: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Classes of chemo agents

substitute alkyl groups for H atoms forming DNA adducts

2 functional groups which can form inter / intra strand crosslinks in DNA

3) Alkylating agents

Page 19: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Nitrogen mustard derivativescyclophosphamide, chlorambucil, melphalan ethyleneimine derivatives thiotepanitrosoureas BCNU, CCNU alkyl sulphonates busulphan

3) Alkylating agents - examples

Page 20: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Cyclophosphamidetrade name: Cytoxan®

Metabolic activation of cyclophosphamide creates guanine adducts that block cell proliferationUsed in combination with methotrexate and 5-FU against several cancers including breast, colon, ovarian and lung cancers.

3) Alkylating agents - examples

Cisplatin

forms adducts at N-7 position of purines creating inter or intrastrand crosslinks that disrupt DNA synthesis.

Effective against ovarian and testicular cancers and has minimal effects on the bone marrow

Page 21: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Classes of chemo agents

Vinca alkaloids like vincristine, vinblastine & paclitaxel, prevent tubulin polymerisation resulting in mitotic arrest

4) Plant alkaloids

Taxol (a terpene from yew trees) causes a similar effect by preventing tubulin depolymerisation. Used against testicular and ovarian cancers and leukaemias

Page 22: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Drug resistance

individual differences in chemosensitivity in cancer patients

leads to accruing resistance during treatment.

Several genetic factors influence the chemosensitivity of cancer cells, including genes involved in drug uptake and secretion, drug metabolism, DNA repair and apoptosis

Page 23: Cancer therapy - conventional Surgery Radiotherapy Chemotherapy Adjuvant therapies.

Hormone therapy Hormone sensitive cancers (Breast

cancer in females and prostate cancer in males) are susceptible to deprivation of the corresponding mitogenic hormone.

E.g. Treatment of involves either

direct inhibition of steroid synthesis : E.g. using either LHRH superagonists or aromatase inhibitors in breast cancer

blocking their effects at the target cell level through the receptors: Steroid receptor antagonists block receptor activity. E.g. tamoxifen is an oestrogen receptor antagonist. Problems with hormone therapy include sexual dysfunction (e.g.ovulation), secondary cancers etc