this presentation is about cancer and anti cancer drugs and presented by me in college.

2. Anti cancer or neoplastic
drugs
Instructor: Dr. Homan “Mohib"
Pharmacology presentation
Prepared By: Nasir Ahmad Danish

3. ANTI NEOPLASTIC DRUGS
Subtitle

4. Discussable topics

5. NUM CONTENT SLIDE
1 INTRODUCTION/DIFINTION
2 EPIDEMIOLOGY OF CANCER
3 RISK FACTORS
4 CHARACTERISTIC OF CANCER
5 THE SEVEN WARNING SIGNS OF CANCER
6 CANCER TYPES
7 CELL CYCLE
8 CARCINOGENESIS
FORMATION OF MALIGNAT CELL BY MUTATION
10 TREATMENT OPTIONS OF CANCER
11 DIAGNOSIS OF CANCER
12 CELL CYCLE SPECIFIC /NON- SPECIFIC DUGS
13 ANTI CANCER DRUG CLASSIFICATION
14 CHEMOTHERAPEUTIC DRUGS AFFECTING RNA /DNA PRECURSORS
15 COMPARISON OF MYELOSUPPRESSIVE POTENTIAL OF
CHEMOTHERAPEUTIC DRUGS
16 MECHANISAM OF ANTICANCER DRUGS
17 TOXIC EFFECTS OF ANTI CANCER DRUGS
18 CONCLUSION.

6. INTRODUCTION/DIFINTION
• Cancer is the rapid creation of abnormal cells that grow beyond their
usual boundaries, and which can then invade adjoining parts of the
body and spread to other organs. This process is referred to as
metastasis. Metastases are the major cause of death from cancer.
(WHO)
• Cancer known medically as a malignant neoplasm, is a broad group
of diseases involving unregulated cell growth. In cancer, cellsdivide
and grow uncontrollably, forming malignant tumors, and invading
nearby parts of the body. The cancer may also spread to more
distant parts of the body through the lymphatic system or blood
stream.
• Not all tumors are cancerous; benign tumours do not invade
neighbouring tissues and do not spread throughout the body. There
are over 200 different known cancers that affect humans.

7. Creeping =crab

8. Anti neoplastic
A=Anticancer drugs cause
N=Nausea and vomiting
T=Treatment regimen must be followed
I=Individualized dosage
N=New drugs appear on the market
E=Exposure time kept to a minimum
O=Only a physician can administer
P=Protect yourself
L=Look, listen, and learn
A=Assessment of laboratory tests
S=Safe dosage based on weight
T=Toxicities
I=Inform patients
C=Classification of agents

9. 9
EPIDEMIOLOGY OF CANCER

11. 11
RISK FACTORS
1. Tobacco
2. Age
3. Sunlight
4. Ionizing radiation
5. Certain chemicals and other substances
6. Some viruses and bacteria
7. Certain hormones
8. Family history of cancer
9. Alcohol
10. Poor diet, lack of physical activity, or being overweight

17. 17
Cancer arises as a result of a series of genetic and epigenetic changes,
the main genetic lesions being:
1. inactivation of tumour suppressor genes
2. the activation of oncogenes (mutation of the normal genes controlling
cell division and other processes).
Cancer cells have four characteristics that distinguish them from normal
cells:
1. uncontrolled proliferation
2. loss of function because of lack of capacity to differentiate
3. invasiveness
4. the ability to metastasise.
Cancer cells have uncontrolled proliferation because of changes in:
1. growth factors and/or their receptors
2. intracellular signalling pathways, particularly those controlling the
cell cycle and apoptosis
3. telomerase expression
4. tumour-related angiogenesis
CHARACTERISTIC OF CANCER

19. THE SEVEN WARNING SIGNS OF
CANCER
The American Cancer Society uses the word C-A-U-T-I-O-N to help recognize
the seven early signs of cancer:
1. Change in bowel or bladder habits
2. A sore that does not heal
3. Unusual bleeding or discharge
4. Thickening of breast tissue or a lump in, testicles, or elsewhere.
5. Indigestion or difficulty swallowing
6. Obvious change in the size, color, shape, or thickness of a wart, mole, or
mouth sore
7. Nagging cough or hoarseness
19

22. 22
categorized based on the functions/locations of the
cells from which they originate:
 Carcinoma: a tumor derived from epithelial cells, those
cells that line the surface of our skin and organs (80-90% of
all cancer cases reported)
 Sarcoma: a tumor derived from muscle, bone, cartilage, fat
or connective tissues.
 Leukemia: a cancer derived from white blood cells or their
precursors.
 Lymphoma: a cancer of bone marrow derived cells that
affects the lymphatic system.
 Myelomas: a cancer involving the white blood cells
responsible for the production of antibodies (B
lymphocytes)
CANCER TYPES

23. Methods of treatment
1. Local treatment(1/3)
1. Surgery
2. radiotherapy
2. General treatment
1. chemotherapy
3. Sever local
treatment
1. Chemotherapy +
radiotherapy
Chemotherapy
– Primary inductive
therapy(SDM-NOT
OTHER THERAPY)
– Primary new helper
therapy(local cancer
and surgical
/radiotherapy are not
benefit.chemotherapy+
radiotherapy
– Maybe done at the
same time or sepratly

24. CANCER CELL CYCLE
KINETICS
A. Cell Cycle Kinetics
B. The Log-Kill Hypothesis

25. Cell Cycle Kinetics
A. Cell Cycle Kinetics
Cancer cell population kinetics and
the cancer cell cycle are important
determinants of the actions and
clinical uses of anticancer drugs.
1. cell cycle-specific [CCS] drugs)
2. cell cycle-nonspecific [CCNS]
drugs
CCS drugs are usually most effective
when cells are in a specific phase of
the cell cycle .
Both types of drugs are most
effective when a large proportion of
the tumor cells are proliferating (ie,
when the growth fraction is high).

26. B. The Log-Kill Hypothesis
1. Cytotoxic effect of anticancer drug follows
killing of logarithmic cell….
2. Drug when meet a constant or specific amount
of cells-so will destroy a specific amount of cell
3. For exa:if a drug 3 log of carcinogen cell
4. So burden of tumor will decrease from 1010 to
107----105 to 102----
5. Rule is due to a relation
6. So this is the rule of chemotherapy

27. The Log-Kill Hypothesis
1. DARK BLUE LINE: Infrequent
scheduling of treatment courses with
low (1 log kill) dosing and a late start
prolongs survival but does not cure the
patient (i.e., kill rate < growth rate)
1. LIGHT BLUE LINE: More intensive
and frequent treatment, with adequate
(2 log kill) dosing and an earlier start is
successful (i.e. kill rate>growth rate)
2. GREEN LINE: Early surgical removal
of the primary tumour decreases the
tumour burden. Chemotherapy will
remove persistant secondary tumours,
and the total duration of therapy does
not have to be as long as when
chemotherapy alone is used.

28. Combination rule of drugs
A. Uses of drugs
only(choriocarcinoma
and burkitt lymphoma)
B. In other case
combination regime..
A. High killing of CC
B. Increase an broad
interaction between drugs
and tumor cell with a
differ genitical in a differ
population turmeric cells.
C. Prevention from future
drug resistant .
• Rule in selection of
drugs combination:
1. tumor sensitive
2. Toxicity
3. Timing and dosage
4. Mechanism of
interaction(for high
effect)
5. Prevent from optional
changing (without Dr
consult)

29. Pharmacokinetic of Anticancer
Agents

30. Resistance
Intrinsic and Acquired
A. Intrinsic:
Some tumor types, e.g. malignant melanoma, renal cell
cancer, and brain cancer, exhibit primary resistance, i.e.
absence of response on the first exposure, to currently
available standard agents(p53 mutation-uncomplete
reparing)
B. Acquired:
– Single drug: change in the genetic apparatus of a given tumor
cell with amplification or increased expression of one or more
specific genes
– Multidrug resistance:
• Resistance to a variety of drugs following exposure to a single
variety of drug
• increased expression of a normal gene (the MDR1 gene) for a cell
surface glycoprotein (P-glycoprotein) involved in drug efflux

31. Normal Cell
DNA Damage
Mutations in the genome
of somatic cells
Alteration of genes that
regulates apoptosis
Expression of altered gene products
Loss of regulatory gene product
MALIGNANT NEOPLASM
Activation of
growth promoting
oncogene
Inactivation of cancer
suppressor genes
Acquired
(environmental DNA
damaging agents)
Chemicals
Radiation
viruses
Successful DNA repair
Failure of DNA repair
CARCINOGENESIS
•Clonal expansion
•Additional mutations
•Heterogeneity

32. Go – Resting phase
Restriction checkpoint
8hrs or more
6-8 hrs
2-5 hrs

33. ANTI CANCER DRUGS

34. CELL CYCLE SPECIFIC /NON- SPECIFIC DUGS
CON…
34

36. 36
MECHANISAM OF ANTICANCER DRUGS
1. Alkylating agents and related compounds, which act by
forming covalent bonds with DNA and thus impeding
replication .
2. Antimetabolites, which block or subvert one or more of the
metabolic pathways involved in DNA synthesis
3. Cytotoxic antibiotics, i.E. Substances of microbial origin that
prevent mammalian cell division
4. Plant derivatives (vinca alkaloids, taxanes, campothecins) -
most of these specifically affect microtubule function and
hence the formation of the mitotic spindle.
5. Hormones, of which the most important are steroids, namely
glucocorticoids, oestrogens and androgens, as well as drugs
that suppress hormone secretion or antagonise hormone
action.

37. CHEMOTHERAPEUTIC DRUGS AFFECTING RNA /DNA PRECURSORS.
37

38. Anti metambolit -Pyrimidine antagonists
Fluorouracil （5-Fu）
Mechanism: convert to 5F-dUMP and inhibit thynidylate
synthase,block the synthesis of dTMP
Clinical uses: good effect on cancer of digestive tract, breast
cancer
Toxicity : myelosuppression and mucositis
Dose: 1 gm orally on alternative days.
Branded Name: Fluracil, five fluro250 mg cap, 5 ml for i.v. inj.
Cytarabine （Ara-C ）
Ara-C →Ara-CMP →→Ara-CTP, competitively inhibit DNA
polymerase. The triphosphate of Cytarabine is an inhibitor of
DNA polymerase.
Clinical uses: acute granulocytic leukemia, mononuclearcyte
leukemia
Toxicity: severe myelosuppression , nausea etc
Dose: 1.5-3 mg/kg i.v. BD for 5-10 days
Branded Name: Cytarabine, cytosar & cytabin 100, 500, 1000 mg
inj.

40. Antimetabolites
 Mercaptopurine & thioguanine:
Converted into monoribonucleotides which inhibit the
conversion of IMP to adenine & guanine nucleotide.
Uses: acute leukemia & solid tumors
Dose: 6- Mercaptopurine – 2.5 mg/kg/day
6 Thioguanine: 100-200 mg/ day
Toxicity : myelosuppression and gastrointestinal symptoms
Generic: Purinethol, Empurine – 50 mg Tab

42. Alkylating agents
HN
N N
N
R
O
H2N
Guanine in DNA
R-X HN
N N
N
R
O
H2N
R
HN
N N
N
R
O
H2N
R
HN
N N
N
R
O
H2N
R
Produce Highly reactive carbonium Ion
which transfer alkyl group to position 7
of guanine by the covalent bond.

43. Cyclophosphamide:
• Supress DNA by its methabolite.
• Usage: CLL-SOLID TUMOR AND LYPHOMA
• SIDE EFFECT: Hemorrhagic inflammation in bladder
Intereuption-fluid therapy in 24-48 will prevent of this
effect
Contra indication: pregenency and lactation
Caution :renal and liver problem
• Dose: Oral - 2-3 mg/kg/day, i.v. – every 10-15 mg/kg,
i.m. – 7-10 mg/kg/day
• Branded Name: Endoxan, Cycloxan 50 mg tab, 200, 500,
1000 mg inj.

44. Cytotoxic drugs
Doxorubicin & Daunorubicin
1. Mechanism : Bind with high affinity to DNA through
intercalation and then block the synthesis of DNA and
RNA
2. Clinical uses
1. One of the most important anticancer drugs ,
treatment of carcinoma of the breast, endometrium,
ovary, testicle, thyroid, lung and many sarcoma,
acute leukemia, Hodgkin’s disease
2. Daunorubicin: acute leukemia
3. Dose: Doxorubicin 60-75 mg slow i.v. inj. every 3 weeks.
4. Daunorubicin: 30-60 mg daily for 3 days repeat weekly.
5. Branded Name: Daunocin 20 mg/vial inj

46. Vinka Alkaloids
Mechanism of action
Bind specifically to the micro tubular protein
tubulin in dimeric form, terminate assembly of
microtubules and result in mitotic arrest at
metaphase, cause dissolution of the mitotic
spindle and finally interfere with chromosome
segregation.

47. Vincristine:
• Use: in childhood acute leukemia, Hodgkin's disease,
wilm’s tumor(nephroblastoma), ewing’s sarcoma &
carcinoma lung.
• Dose: 1.5-2 mg/m2 BSA i.v. weekly
• Generic: Oncovin & cytocristin 1 mg/ vial inj
• Side effect: constipitation,abdomen swallow,loss deep tendon
reflex
• Contra indication:pregenancy and lactation

48. 48
Tamoxifen binds to the estrogen
receptor and the complex fails to
induce estrogen-responsive genes, and
RNA synthesis does not ensue.
 The result is depletion (down-
regulation) of estrogen receptors, and
the growth-promoting effects of the
natural hormone and other growth
factors are suppressed.
The action of tamoxifen is not related
to any specific phase of the cell cycle.
Usage :breast cancer
Contra indication:pregenancy
Side effect:bright or
hotness,hypercalcemis,ovary
cyst,emboli with cytotoxic drugs
MECHANISM OF ACTION OF TAMOXIFEN

49. 49
1. Bone marrow toxicity (myelosuppression) with
decreased leucocyte production and thus
decreased resistance to infection
2. Impaired wound healing
3. Loss of hair (alopecia)
4. Damage to gastrointestinal epithelium
5. Depression of growth in children
6. Sterility
7. Teratogenicity
TOXIC EFFECTS OF ANTI CANCER DRUGS

50.  Acute toxicity
 Vomiting
 Allergic reactions
 Arrhythmias
 Delayed effects
 Mucositis
 Alopecia
 Bone marrow suppression
 Chronic toxicities
 Heart
 Kidney
 Liver
 Lungs 50

51. Causes of weight loss
Weight loss often begins
with appetite loss. This may result from the
following side
effects of cancer or treatment:
1. Changes to the immune system or metabolism.
Metabolism is the body’s process of breaking down
food and turning it into energy.
1. Nausea and vomiting
2. Constipation
3. Mouth sores
4. Difficulty chewing
5. Difficulty swallowing
6. Loss of taste
7. Depression
8. Pain

52. 52
CONCLUSION
1. Every year, more than 1 million Americans and more than 10
million people worldwide are expected to be diagnosed with cancer,
a disease commonly believed to be preventable.
2. Only 5–10% of all cancer cases can be attributed to genetic
defects, whereas the remaining 90–95% have their roots in the
environment and lifestyle.
3. The evidence indicates that of all cancer-related deaths, almost
25–30% are due to tobacco, as many as 30–35% are linked to diet,
about 15–20% are due to infections, and the remaining percentage
are due to other factors like radiation, stress, physical activity,
environmental pollutants etc.
4. Therefore, cancer prevention requires smoking cessation,
increased ingestion of fruits and vegetables, moderate use of
alcohol, caloric restriction, exercise, avoidance of direct exposure
to sunlight, minimal meat consumption, use of whole grains, use of
vaccinations, and regular check-ups.

53. References
1. www.journals.elsevier.com/cancer-epidemiology
2. robboins Basic pathology-9th edition
3. www.medicinenet.com/cancer_causes/page6.htm
4. www.retireeasy.com/health/7-warning-signs-of-cancer
5. Clinical pharmacology and drug treatment
6. Basic and clinical pharmacology {Bertram G.Katzung}-2015-
13th edition
7. Medscape.com
8. Wekipedia.com

54. ?

55. ‫قدس‬ ‫طایر‬ ‫ای‬‫کن‬ ‫راه‬ ‫بدرقه‬ ‫همتم‬‫که‬
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