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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.
Electromagnetic radiation
intranuclear
Xtranuclear
Radiotherapy
X-ray source
Radiotherapy sources
Biological effects
Rad is the unit of absorbed dose
1 rad =100erg/g
Gy (Gray)
1 Gy = 100rads = joule/kg
Conformal radiotherapy
Advances in imaging techniques
E.g. Liver tumours
Time, Dose, Fractionation
Adjuvant radiotherapy
Boron Neutron Capture Therapy
Adjuvant radiotherapy
Thermotherapy
MR-guided laser
induced
thermotherapy of
osteiod osteoma
Adjuvant radiotherapy
Photodynamic therapy
Adjuvant radiotherapy
Bioreductive drug adjuvant therapy
Harmless prodrug
Under certain conditions is converted to a cytotoxic
metabolite
E.g. AQ4N (alkylaminoanthraquinone N-oxide)
Harmless in oxic cells
Converted into cytotoxic AQ4 in hypoxic cells
combined with radiotherapy or chemotherapy
Chemotherapy
Works by affecting DNA synthesis and function
Classes of chemo agents
1) Antimetabolites:
Methotrexate, 5-fluorouracil, cytosine arabinoside, 6mercaptopurine
Analogues of normal metabolites
Function in 3 ways
Substitution
Competition for catalytic site
Competition for regulatory site
antimetabolites
serine hydroxymethyltransferase (SHMT)
thymidylate synthase (TS)
dihydrofolate reductase (DHFR)
methotrexate
Folic acid antagonist
Dihydrofolate reductase
Reduced synthesis of A & G
Cytotoxicity reversed by leucovorin
choriocarcinoma
Classes of chemo agents
2) Antibiotics
Bacterial or fungal derivatives that affect cellular
processes like DNA or protein synthesis
Topoisomerase inhibitors
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
Classes of chemo agents
3) Alkylating 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 - examples
Nitrogen mustard derivatives
cyclophosphamide, chlorambucil, melphalan
ethyleneimine derivatives
thiotepa
nitrosoureas
BCNU, CCNU
alkyl sulphonates
busulphan
3) Alkylating agents - examples
Cyclophosphamide
trade name: Cytoxan®
Metabolic activation of cyclophosphamide
creates guanine adducts that block cell
proliferation
Used in combination with methotrexate and
5-FU against several cancers including
breast, colon, ovarian and lung cancers.
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
Classes of chemo agents
4) Plant alkaloids
Vinca alkaloids like
vincristine, vinblastine &
paclitaxel, prevent tubulin
polymerisation resulting in
mitotic arrest
Taxol (a terpene from yew
trees) causes a similar
effect by preventing
tubulin depolymerisation.
Used against testicular
and ovarian cancers and
leukaemias
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
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