Anti cancer Drugs
Dr. Mobasher Ahmad
Cancer chemotherapy: general
• The term ‘cancer’ refers to a malignant neoplasm (new
• Cancer cells can manifest :
Un controlled proliferation (no differentiation)
the ability to metastasise
. Most anticancer drugs are antiproliferative and will also
affect rapidly dividing normal cells, and are thus likely to
depress bone marrow, to impair healing, to depress growth,
to cause sterility and hair loss, and to be teratogenic. Most
cause nausea and vomiting.
Drugs used in cancer
• Cytotoxic drugs:
• Alkylating agents: These act by forming covalent bonds
with DNA and thus impeding DNA replication.
• Antimetabolites: These block or subvert one or more of
the metabolic pathways involved in DNA synthesis.
• Cytotoxic antibiotics: These are substances of microbial
origin which prevent eukaryotic cell division.
• Vinca alkaloids: These are substances of plant origin that
specifically affect microtubule function and hence the
formation of the mitotic spindle.
Most important are steroids, namely
glucocorticoids, oestrogens and androgens.
Sites of action of cytotoxic agents
that act on dividing cells
• Purine and Pyrimidine synthesis
• 6- Mercaptopurine, Thioguanine
Inhibit purine sysnthesis, inhibit
Methotrexate: inhibition of dihydrofolate
Reductase leads to an inhibition of
purine ring and dTMP biosysthesis
Terminates DNA chain elongation.
Incorporated into DNA and RNA
resulting in altered function of nucleic acids.
Scission of DNA by an oxidative process.
• Dactinomycin,Doxorubicin, Daunorubicin
• Intercalate with DNA, disrupting DNA function.
• Alkylating agents Nitrosoureas Cisplatin
• Alter structure and function of DNA by
cross-linking and or fragmenting of DNA strands.
Anticancer drugs: alkylating
agents and related compounds
• Alkylating agents have alkyl groups which can form
covalent bonds with cell substituents;a carbonium ion is
the reactive intermediate.
• Most have two alkylating groups and can cross link two
nucleophilic sites such as the N7 of guanine in DNA;
cross-linking can cause :
.pairing of alkylguanine with thymine, and
then substitution of At for GC
.Excision of guanine and chain breakage.
The principal effect occurs during DNA synthesis.
• Unwanted effects include myelosuppression, sterility and risk of non-
• The main alkylating agents are: Nitrogen mustards: e.g
cyclophosphamide, which is activated to give aldophosphamide, which
is then converted to phosphoramide mustard and acrolein.
Cyclophosphamide myelosuppression affects particularly the
lymphocytes. Given orally.
• Nitrosoureas: e.g lomustine may act on non-dividing cells;can cross
the blood-brain barrier; causes delayed, cumulative
• Cisplatin; It interacts with DNA;it has low myelotoxicity but causes
severe nausea and vomiting and can be nephrotoxic. Given
Anticancer drugs: antimetabolites
• These drugs block or subvert pathways in DNA synthesis.
• Folate antagonists: Methotrexate inhibits dihydrofolate
reductase, preventing generation of tetrahydrofolate; the
main result is interference with thymidylate synthesis.
Methotrexate is taken up into cells by the folate carrier,
and like folate, converted to the polyglutamate form. Given
orally. Normal cells affected by high doses can be rescued
by folinic acid.(Folate—FH2---FH4----MethyleneFH4—
Deoxythymidylic acid Methionine)
Unwanted effects: myelosuppression,possible
• Pyrimidine analogues: Fluorouracil, given orally or
intravenously, is converted to a fraudulent nucleotide and
inhibits thymidylate synthesis.
• Cytarabine, given intravenously or subcutaneously; its
triphosphate form inhibits DNA polymerase; potent
• Purine analogues: Mercaptopurine, given orally, is
converted into a fraudulent nucleotide.
Anticancer drugs: cytotoxic
• Doxorubicin : It inhibits DNA and RNA synthesis; the DNA effect is
due to interference with topoisomerase ll action. Given by intravenous
infusion; it is excreted mainly in bile. Unwanted effects: nausea and
vomiting, myelosuppression, hair loss; it is cardiotoxic in high doses.
• Biomycin: It causes fragmentation of DNA chains. It can act on non-
dividing cells. Given by injection. Unwanted effects: fever,allergies,
pulmonary fibrosis. Virtually no myelosuppression.
• Dactinomycin: It intercalates in DNA, interferes with RNA
polymerase and inhibits transcription. Given by injection. Unwanted
effects: nausea and vomiting, myelosuppression.
• Mitomycin : It is activated to give an alkylating metabolite. Given
Anticancer drugs: miscellaneous
• Plant alkaloids: Vincristine It inhibits mitosis at
metaphase by binding to tubulin. Given by injection.
Relatively non-toxic, but can cause unwanted
• Hormones: These are used in hormone-sensitive tumours:
Glucocorticoids for leukaemias and
lymphomas.Oestrogens for tumours in men. Androgens
or tamoxifen for breast tumours.
• Radioactive isotopes: It can be targeted at specific
tissuese. E.g I 131 for thyroid tumours.
• Malignant disorders of blood leukocytes.
• Support the patient with red cell and platelet
• Remission induction chemotherapy and
• Remission induction chemotherapy: The objective is
to clear the body of all detectable leukemic leukocytes.
The current practise is to employ a combination of
vincristine and prednisone for initial induction of
• Maintenance Chemotherapy: The objective of
maintenance therapy is to keep the population of residual
leukemic cells in check so that they do not repopulate the
blood and bone marrow and lead to the return of
• This usually consists of a combination of oral
methortrexate, mercaptopurine and cyclophosphamide,
administered either in pulses, simultaneously, or in various
Treatment for HBV
• HBV infected persons should be evaluated by
their doctor for liver disease.
• Adefovir dipivoxil, interferon alfa-2b,
pegylated interferon alfa-2a, lamivudine, and
entecavir are five drugs used for the
treatment of persons with chronic hepatitis B.
• These drugs should not be used by pregnant
• Drinking alcohol can make your liver disease