This document summarizes various types of anti-cancer drugs and their mechanisms of action. It discusses how chemotherapy drugs like alkylating agents and antimetabolites target rapidly dividing cancer cells by damaging DNA or interfering with DNA synthesis. Newer targeted therapies include monoclonal antibodies that target specific proteins in cancer cells or hormone therapies that block estrogen production in breast cancer. The document also outlines how different drug classes like plant alkaloids, antibiotics, and topoisomerase inhibitors damage DNA or disrupt cell division to kill cancer cells.

1. ANTI-CANCER
DRUGS AND THEIR
MECHANISM OF
ACTION

2. Cancer
 Cancer is a disease in which the cells
divide and grow uncontrollably and rapidly
forming tumors.
 Cancer is thought to be caused by tobacco
use, certain infections, radiation, lack of
physical activity, obesity and by the
interaction between genetic susceptibility
and environmental toxins.
 There are over 200 different known cancers
that afflict humans

3. Chemotherapy
 Chemotherapy is the treatment of cancer
with one or more cytotoxic antineoplastic
drugs . Traditional chemotherapeutic agents
act by killing cells that divide rapidly, one of
the main properties of most cancer cells.
This means that chemotherapy also harms
cells that divide rapidly under normal
circumstances.

4. Targeted therapy
 This results in the most common side-
effects of chemotherapy: myelosuppression
(decreased production of blood cells),
mucositis (inflammation of the lining of the
digestive tract) and alopecia (hair loss).
 Some newer anticancer drugs (monoclonal
antibodies) are not indiscriminately
cytotoxic, but rather target proteins that are
abnormally expressed in cancer cells and
that are essential for their growth. Such
treatments are often referred to as targeted
therapy

5. Types of anticancer drugs
 According to the source of drugs,the majority
of chemotherapeutic drugs can be divided in
to
 Alkylating agents,
 Antimetabolites,
 Antibiotics,
 Plant alkaloids,
 Topoisomerase inhibitors and
 Other antitumour agents.
 Some newer agents do not directly interfere
with DNA. These include monoclonal
antibodies and the new tyrosine kinase
inhibitors

6. Mechanism of anticancer
drugs
 Block nucleic acid (DNA, RNA)
biosynthesis
 Directly destroy DNA and inhibit DNA
reproduction
 Interfere transcription and block RNA
synthesis
 Interfere protein synthesis and function
 Influence hormone homeostasis

7. Alkylating agents
 Alkylating agent used in cancer treatment
attaches an alkyl group to DNA. It forms a
covalent bond with the nucleophilic
substanceThe nitrogen at position 7(N7) of
guanidine residues in DNA is strongly
nucleophilic and is especially susceptible.Other
molecular sites such as N1 and N3 of adenine
and N3 of cytosine may also be effected.It lead
to
 Cross linking of bases
 Abnormal base pairing &
 DNA strand breakage

8. Antimetabolites
 Antimetabolites are structurally
related to normal componente of DNA.
They prevent these substances from
becoming incorporated in to DNA
during the "S" phase of the cell cycle
by competing with the purines and
pyrimidines in DNA or RNA synthesis
which in turn stops the normal
development and division.

9. Methotrexate(Abitrexate®)
 Methotrexate is the most widely used
antimetabolite in cancer
chemotherapy. It mainly acts by
inhibiting the enzyme dihydro folate
reductase(DHFR),which is essential in
the conversion of folate to THF and
lack of the co enzyme THF leads to
inhibition of DNA synthesis

10. 6-Mercaptopurine(Purinethol®)
 6-Mercaptopurine is an analogue of purine
inhibits purine nucleotide synthesis and
metabolism and is highly effective
anticancer drug.
 It is a purine analogue of the nucleobase
guanine. It incorporates into DNA during the
synthesis phase (S-phase) of the cell
resulting in the DNA synthesis inhibition
Tioguanine

11. 5-Fluorouracil(Adrucil®)
 5-Fluorouracil is an analogue of
uracil(pyrimidine) that lead to the inhibition of
DNA. It acts as a thymidylate synthase
inhibitor. Interrupting the action of this
enzyme blocks synthesis of the pyrimidine
thymidine, which is a nucleoside required for
DNA replication

12. Hydroxyurea(Hydrea®)
It is an antineoplastic drug that
reduces the production of
deoxyribonucleotides through the
inhibition of the enzyme
ribonucleotide reductase that
catalyzes the formation of
deoxyribonucleotides from
ribonucleotides

14. Plant alkaloids
 Mitotic spindles are very important
because they help to split the newly
copied DNA such that a copy goes to
each of the two new cells during cell
division. These drugs disrupt the
formation of these spindles and
therefore interrupt cell division
Vincristine

15. Vinca alkaloids-Vinblastine (Velban®),
Vincristine (Oncovin®)
 Binds to the microtubular protein tubulin
in a dimeric form
 The drug-tubulin complex adds to the
forming end of the microtubules to
terminate assembly
 Depolymerization of the microtubules
occurs
 Resulting in mitotic arrest at metaphase,
dissolution of the mitotic spindle, and
interference with chromosome
segregation

16. Topoisomerase inhibitors
 Topoisomerases are essential enzymes
that maintain the topology of DNA.
Inhibition of type I or type II
topoisomerases interferes with both
transcription and replication of DNA by
upsetting proper DNA supercoiling.
 Some type I topoisomerase inhibitors
include camptothecins: irinotecan and
topotecan.
 Examples of type II inhibitors include
podophyllotoxins,

17. Antibiotics
Actinomycin
 It is isolated from soil bacteria of the genus
Streptomycescell biology, Actinomycin D is
shown to have the ability to inhibit
transcription. It does this by binding DNA at
the transcription initiation complex and
preventing elongation of RNA chain by RNA
polymerase

18. Anthracyclines
 Anthracyclines are a class of drugs
(CCNS or cell-cycle non-specific)[1] used
in cancer chemotherapy derived from
Streptomyces bacterium. nhibits DNA
and RNA synthesis by intercalating
between base pairs of the DNA/RNA
strand, thus preventing the replication of
rapidly-growing cancer cells.[6] Inhibits
topoisomerase II enzyme, preventing the
relaxing of supercoiled DNA and thus
blocking DNA transcription and

19. Dactinomycin
 Binds to double stranded DNA through
intercalation between adjacent guanine-
cytosine base pairs
 Inhibits all forms of DNA-dependent RNA
synthesis
 Binds to DNA through an antibiotic-Mg2+
complex
 This interaction interrupts DNA-directed RNA
synthesis
Plicamycin

20. Bleomycin
 It is a drug used in cancer chemotherapy. It
is an anthracycline antibiotic Doxorubicin
interacts with DNA by intercalation and
inhibition of macromolecular
biosynthesis.This inhibits the progression of
the enzyme topoisomerase II, which relaxes
supercoils in DNA for transcription
 Bleomycin acts by induction of DNA strand
breaks
Doxorubicin(Adriamycin®)

21. Hormone therapy
Aromatase inhibitors
 Aromatase inhibitors are an important
class of drugs used for the treatment of
breast cancer
 At menopause, estrogen production in
the ovaries ceases, but other tissues
continue to produce estrogen through
the action of the enzyme aromatase.
When the action of aromatase is
blocked, estrogen levels in post-
menopausal women can drop to
extremely low levels, causing growth
arrest and/or apoptosis of hormone-
responsive cancer cells

22. MONOCLONAL ANTIBODIES
 Monoclonal antibodies such as
Rituximab and Trastuzsumab are also
used in the cancer chemotherapy.
 This antibodies activate the host
immune mechanism and kills the
cancer cells.

23. RADIOACTIVE ISOTOPES
 Radioactive isotopes are used in the
treatment of certain tumours by their
property of producing ionization in the
cells,thereby causing cell destruction.
 Eg.Radioactive Iodine is used in
thyroid carcinoma

24. Some drugs are
Cell Cycle Nonspecific Agents (CCNSA)
drugs that are active throughout the cell cycle
 Alkylating Agents
Antibiotics
Cell Cycle Specific Agents (CCSA)
drugs that act during a specific phase of the
cell cycle
S Phase Specific Drug:
Aantimetabolites, Topoisomerase Inhibitors
M Phase Specific Drug:
Vinca Alkaloids, Taxanes
G2 Phase Specific Drug:
Bbleomycin