Tamoxifen is an anti-estrogen drug used to treat breast cancer. It works by competitively binding to estrogen receptors in cells, inhibiting estrogen's ability to stimulate cancer growth. Tamoxifen decreases production of growth factors like TGF-β and IGF-1 that promote cancer cell growth. It is also used to treat other cancers driven by estrogen and can help prevent osteoporosis and heart attacks. Side effects include menstrual irregularities and vaginal bleeding. Anti-androgens block androgen receptors in prostate cancer cells and are used to treat prostate cancer. L-asparaginase treats acute lymphoblastic leukemia and lymphomas by depriving cancer cells of the amino acid asparagine

1. Anti-hormonal anti-
cancer drugs
DR. HAFIZ MUHAMMAD IRFAN
ASSISTANT PROFESSOR

2. Anti-estrogen
Tamoxifen
 Tamoxifen is a competitive inhibitor of estradiol binding to the
estrogen receptor (ER).
 After binding to the ER, tamoxifen induces a change in the
three dimentional shape of the receptor, inhibiting its binding
to the estrogen responsive element on DNA.

3. Tamoxifen….....
 Under normal physiological condition, estrogen stimulation
increases tumor cell production of transforming growth factor
β (TGF-β).
 By blocking these pathways, the net effect of tamoxifen
treatment is to decrease the autocrine stimulation of breast
cancer growth.
 Tamoxifen also decreases the local production of insulin-like
growth factor-1 by surrounding tissues. It is a growth factor for
cancer cells.

4. Tamoxifen…….
 Tamoxifen is extremely useful for the treatment of breast
cancer.
 Also be effective in progesterone-resistant endometrial
cancer.
 Slow the development of osteoporosis.
 Decrease the risk of myocardial infarction.
 Toxicities:
 menstrual irregularities, nausea and vomiting,
 vaginal bleeding

5. Anti-androgens
 Anti-androgens are effective in prostate cancer treatment.
They may be:
 1. Steroidal anti-androgen(SAA) -Cyproterone acetate,
Megestrol acetate
 2. Non-steroidal anti-androgens(NSAA)--Flutamide,
Nilutamide
 SAA are weak partial agonists and competitive inhibitors of
the androgen receptor in target tissues.
 ADRs: They cause loss of libido, decreased sexual potency
and low testosterone level.

6. Anti-androgen…………
 NSAA inhibit translocation of the androgen receptor to the
nucleus from the cytoplasm of target cells and induce anti-
proliferating effect in prostate cancer.
 Flutamide was the first androgen receptor antagonist. It is
metabolized into alpha-hydroxyl flutamide (more potent than
parent drug).
 Side effects include diarrhea, emesis, reversible liver
abnormalities.

7. L-Asparaginase
 Normal tissues synthesize L-asparagine amino acid in the
presence of asparagine synthetase in sufficient amount for
protein synthesis.
 Neoplastic cells are unable to synthesize this amino acid due
to lack of asparagine synthetase enzyme.
 These cells take asparagine from plasma/circulation.

8. L-asparaginase…….
 L-asparaginase anticancer drug deprives neoplastic cells of
asparagine by inhibiting asparagine synthetase enzyme and
convert this into aspartic acid and ammonia.
 This drug in combination with
methotrexate/doxorubicin/vincristine and prednisolone for the
treatment of acute lymphoblastic leukemia and other high
grade lymphomas.
 Resistance against this drug can be developed through
induction of asparagine synthetase in tumors cells.
 Toxicities include: hypersensitivity, hyperglycemia,
hypertriglyceridemia, pancreatitis.

9. Hydroxyurea
 The primary site of action of Hydroxyurea is the enzyme
ribonucleoside diphosphate reductase which catalyzes the
coversion of ribonucleotide to deoxyribonucleotides, a rate
limiting step in the synthesis of DNA.
 The drug specifically target S phase of cell cycle in which the
concentration of this reductase enzyme is maximum.
 By binding to this enzyme, hydroxyurea causes cells to arrest
at G1 to S interface.

10. Hydroxyurea…..
 The specific use is in myelo-proliferative syndrome, chronic
granulocytic leukemia, polycythemia vera and thrombocytosis.
 Also be effective in sickle cell disease.
 Hydroxyurea may also potentiate anti-proliferative effects of
DNA damaging agents such as cisplatin, alkylating agents or
topoisomerase-II inhibitors.
 Toxicities: hematopoitic depression- leukopenia, megaloblastic
anemia, teratogenic