ANTI-CANCER DRUGS

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Done By : Mukul Tambe

CONTENTS

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 Introduction.
 Genesis of a cancer cell.
 Cell cycle.
 Causes.
 Classification of cancers.
 Anti-Cancer drugs classification.
 Mechanism of action.
 References.

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INTRODUCTION
 Cancer is a disease in which there is uncontrolled multiplication

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and spread within the body of abnormal forms of the body’s own
cell.
 There are two types of tumors : 1. Benign tumor

2. Malignant tumor
 Benign tumor : It is not a cancer cell it will not spread to

other cells.
 Malignant tumor : It is a cancer cell which can spread to
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neighboring tissues and enters into blood cells.
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GENESIS OF A CANCER CELL
 A normal cell turns to cancer cell because of one or more

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mutations in its DNA which can inherited or acquired.
 The development of cancer is a complex multistage process,
involving not only more than one genetic change but usually
also other epigenetic factors like hormonal action.
 There are two main categories of genetic change:

1. The activation of proto-oncogenes to oncogenes.

2. The inactivation of tumor suppressor genes.

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Activation of proto-oncogene to oncogene:
 Genes that normally control cell division , apoptosis,
differentiation but converted to oncogenes by viral or

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carcinogen action.

Inactivation of tumor suppressor genes:

 Normal cells contain genes that have ability to suppress the
malignant but due to mutations the loss of tumor suppressor
genes can be critical in carcinogenesis.

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CELL CYCLE
 Go phase : Resting phase.
 G1 phase : Mech. Ensures that

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everything is ready for DNA synthesis.
 S phase : DNA replication occurs
during this phase.
 G2 phase : Mech. Ensures that
everything is ready to enter the Mitosis
phase and divide.
 M phase : Cell growth stops at this
stage. 7
 Cell cycle is regulated by two factors:

1. Positive regulators of cell growth.

2. Negative regulators of cell growth.

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 Increase in positive regulators cause tumor which further divided by
Mutations.
 Negative regulators cause cell injury.
 Cancer cells can manifest from normal cells by following:

1.Uncontrolled proliferation.

2.Dedifferentiation and loss of function.

3.Invasiveness. 8

4.Metastasis.
Normal cell mitosis

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Cancer cell mitosis

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 CAUSES
 Majority cancers(90-95%) are caused by Environmental factors.

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 Remaining (5-10%) are caused by inherited genetics.
 Cancers are caused by some viruses they are Oncoviruses which
include human papiloma virus, Epstein-Barr virus, Hepatitis B
and C virus.
 Some types of bacteria Helicobacter pylori.

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CLASSIFICATION OF CANCER

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 Based on type of cell:
 Carcinoma : Derived from Epithelial cells.
 Sarcoma : Cancer arising from connective tissue.
 Lymphoma and Leukemia : These two classes arise from
hematopoietic cells.
 Germ cell tumor : Arise from pluripotent cells.
 Blastoma : Cancers derived from immature precursor
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cells or embryonic tissue.
ANTI-CANCER DRUGS
                                 Anticancer drugs
                                             

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Cytotoxic Drugs                                   Hormones and 
their 
  (killing the                                            antagonists
Cancer cells)                                          (suppressing the 
                                                               cancer cells by 
                                                                altering the 
                                                                 hormonal 
mileau)
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 Alkylating Agents

Antimetabolites

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Natural Products
Cytotoxic Drugs
Platinum compounds

Monoclonal antibodies

Miscellaneous Agents
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 Alkylating Agents

Nitrogen mustards: Cyclophosphamide, Ifosfamide,

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Estramustine , Melphalan
Chlorambucil, Mechlorethamine.
Ethylenimines : Thiotepa.
Methlmelamine : Altretamine.
Alkyl sulfonates : Busulphan
Treosulfan
Nitrosoureas : Lomustine, Carmustine,
Semustine, Streptozocin.
Triazenes : Dacarbazine , Temozolamide. 18
 Antimetabolites

Folate Antagonist : Methotrexate, Pemetrexed.

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Purine antagonists : 6-mercaptopurine,
6- thioguanine, Azathioprine
Fludarabine, Pentostatin
Cladribine.
Pyrimidine antagonists : 5-fluorouracil
Floxuridine
Cytarabine
Gemcitabine
Capecitabine
Azacitidine 19
 Natural Products

Vinca alkaloids : Vincristine, Vinblastine, Vinorelbine.

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Taxanes : Paclitaxel, Docetaxel
Epipodophyllotoxin : Etoposide, Teniposide.
Camptothecins : Topotecan, Irinotecan.
Enzymes : L- Asparaginase
Antibiotics : Dactinomycin, Doxorubicin, Daunorubicin
Epirubicin, Idarubicin, Aclarubicin,
Bleomycin, Mithramycin, Mitomycin,
Methoxantrone
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 Platinum compounds : Cisplatin, Carboplatin

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Oxaliplatin.
 Monoclonal Antibodies : Transtuzumab, Alemtuzumab

Tositumab, Rituximab, Cituximab

Gemtuzumab, Bevacizumab.
 Miscellaneous Agents : Hydroxyurea, Procarbazine

Interferon-α, Imatinib, Gefitinib

Erlotinib, Bortezomib.
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 Glucocorticoids

Anticorticoids

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Androgens & Antiadrogens
Hormones and
their antagonists Estrogens & Antiestrogens

Progestins

Aromatase inhibitors

Gn RH superagonists 22
 Glucocorticoids : Prednisolone, Dexamethasone.
 Anticorticoid : Aminoglutethimide, Trilostane.
 Androgens : Testosterone, Fluoxymestrone.

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 Antiandrogens : Flutamide, Nilutamide, Bicalutamide,
finasteride, Dutasteride.
 Estrogens : Ethinyl estradiol, Diethylstilbestrol, Fosfestrol.
 Antiestrogens : Tamoxifen, Toremifene, Fluvestrant.
 Progestins : Hydroxyprogesterone acetate, Megestrol,
Norethisterone, Medroxyprogesterone.
 Aromatase inhibitors : Anastrozole, Letrozole, Exemestane.
 Gn RH superagonists : Laprorelin, Naferelin,
Goserelin, Buserelin, Triptorelin.
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MECHANISM OF ACTION

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 Vinca alkaloids and taxanes acts on M phase because of
mitotic spindles formation.

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 Epipodophyllotoxins, Campthothecins, Anti cancer
antibiotics acts on G2 phase.
 Anti metabolites acts on S phase.

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ALKYLATING AGENTS
Formation of Carbonium ion is main step.

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Attacks lone pair of electron in DNA.

Cross linked with DNA.

Most of cytotoxic anticancer alkylating agents are bifunctional

i.e., they have two alkylating groups.

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 Nitrogen mustards :
 Cyclophosphamide is most commonly used alkylating agent.

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 Its is given orally or I.V. and also given through I.M.
 Toxic effects: Nausea.

Vomiting.

Bone marrow depression and

Haemorrhagic cystitis.
 Estramustine is a combination of mustine with an estrogen.
 It has both cytotoxic and hormonal action . 27
 Nitrosoureas:
 They are lipid soluble and cross BBB.

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 Most of nitrosoureas have a severe cummulative depressive
effect on bone marrow that starts 3-6 weeks after initiation of
treatment.
 Alkyl sulfonates :
 Busulphan has a selective effect on bone marrow depressing
the formation of granulocytes and platelets in lower dose and
RBC in higher dose.
 It is used in chronic granulocytic leukaemia. 28
 Triazenes :
 Dacarbazine is a pro drug is activated in liver and the

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resulting compound is subsequently cleaved in the target
cell to release an alkylating derivative.
 Unwanted effects include severe nausea and vomiting.

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ANTI METABOLITES
Pteridine

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Dihydro pteridine

↓Dihydro pteroic acid synthase

Dihydro pteroic acid

↓Dihydro folate reductase.(DHFR)

Dihydro folate

↓DHFR

Tetrahydrofolate

AMP synthase Thymidilate synthase 30

Purines Pyrimidines
 Folate antagonist acts on DHFR and inhibit the formation of
dihydro folate.
 Unwanted effects : Depression of Bone marrow.

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Damage of the epithelium of GIT.
 Pyrimidine antagonists inhibit Thymidilate synthase results in
the inhibition of DNA synthesis.
 Cytarabine inhibit DNA polymerase.
 Unwanted effects: Bone marrow depression.

Nausea.

Vomiting. 31
 Gemcitabine new analogue of cytarabine has unwanted
effects like influenza and mild myelotoxicity.
 Purine antagonist inhibit Adenosine monophosphate

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synthase.
 Fludarabine is metabolised to triphosphate and inhibits DNA
synthesis. It is myelosuppressive.
 Pentostatin has different M.O.A.
 It inhibit adenosine deaminase enzyme which catalyses
deamination of adenosine to inosine.
 It has significant effects on cell proliferation. 32
NATURAL PRODUCTS
 Vinca alkaloids :

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 They act by binding to tubulin and inhibiting its
polymerization into microtubules which prevents the spindle
formation in mitosing cells and causes arrest at metaphase.
 Their effects are only because of changes in mitosis.
 Vincristine has mild myelosuppressive activity but causes
paraesthesias.
 Vinblastine is less neurotoxic but causes leucopenia.
 Vinorelbine is a new Vinca alkaloid. 33
 Taxanes :
 Stabilizes microtubules and inhibit mitosis.

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 Paclitaxel is given by I.V. and Docitaxel is given through
orally.
 These are used in treating Breast cancers.
 Paclitaxel+Carboplatin is the choice of treatment for
Ovarian cancer.
 Unwanted effects: Bone marrow suppression.

Cummulative Nephrotoxicity.
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 Epipodophyllotoxins :
 It acts by inhibiting mitochondrial function and nucleoside

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transport and having effect on Topoisomerase-II.
 Unwanted effects are Nausea, Vomiting, and hair loss.
 Campthothecins :
 These are bind and inhibit Topoisomerase-I.
 Diarrhoea and reversible Bone marrow depression.

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 Anti-Cancer Antibiotics :
 It shows action by inhibiting Topoisomerase-II.

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 Epirubicin is less cardiotoxic than doxorubicin.
 Bleomycin is most effective in G2 phase and mitosis but
it is also active against non dividing cells.
 Mitomycin cross links the DNA and degrade DNA
through the generation of free radicals.

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MONOCLONAL ANTIBODIES
 These are immunoglobulins produced by cell culture to

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react with antigen expressed on cancer cells.
 Rituximab is a monoclonal antibody that attaches to
CD20 protein on B cells and kills complement mediated
lysis.
 Unwanted effects hypertension, chills, and fever during
initial infusion.
 Trantuzumab is a humanised monoclonal antibody.
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 Unwanted effects similar to Rituximab.
PLATINUM COMPOUNDS
 Cisplatin is a water soluble coordination complex

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containing a central platinum atom surrounded by two
chlorine atoms and two ammonia groups.
 It action is similar to alkylating agents.
 When enters the cell chlorine dissociates leaving complex
that reacts with water and interacts with DNA.
 It causes cross linking of DNA.
 Cisplatin given through I.V.
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 It has low myelotoxicity but severe nausea and vomiting.
HORMONES AND THEIR ANTAGONISTS
 Glucocorticoids :

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 It has inhibitory effect on lymphocyte proliferation and used
in leukaemia.
 Tamoxifen used in Breast cancer.
 Gonadotropin releasing hormone analouges are for Breast
cancer and Prostate cancer.
 Anti androgens for Prostate cancer.
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REFERENCES

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 Pharmacology by H.P.Rang and M.M.Dale 5th edition
page no. 693.

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