2. TREATMENT
• BASIC TERMS
• SYMPTOMS & DIAGOSIS
• TYPES OF CANCER
• Oncogens
• How cancer arises
• Genes controling cell cycle
• Statistics
• Different types of treatment
• Classification of drugs
• Log kill hypothesis
• Cell specific non specific drugs
• Resistances
• Adverse reaction
• Widely used and recent drugs
• Synthesis
3. WHAT IS CANCER: it is a class of disease characterized by..
Uncontrolled proliferation of cells.
Dedifferentiation
Loss of funtion
Invasion to local tissues
Spread or metastasis to other parts of the
body.
4. Cancer is not a single disease. It is a group of more than 200
different diseases.
Cancer may spread to other parts of the body.
currently 1 in 4 deaths in USA are due to cancer.
1 in 17 deaths are due to lung cancer.
An estimated 2,22,520 people diagnosed lung cancer in the
United States in 2010.
Lung cancer is the most common cancer in men.
5. Breast cancer is the most common cancer in
women.
Around 15 lakh new cases are diagnosed every
year in india.
A total of 15,96,670 new cancer cases and
5,71,950 deaths from cancer are projected to occur
in the United States in 2011.
7. The medical term for tumor (or) cancer is Neoplasm,
which means a relatively autonomous growth (or)
un corodinated cell proliferation of body tissue.
The term Neoplasm means New growth & the process
of cell proliferation is called Neoplasia.
The branch of medicine which deals with the excessive
study of neoplasm (tumor) and its development
diagnosis and treatment is called “Oncology.”
8. • For the first time Hippocrates coined the Greek word
Karkinos i.e. (crab/cray fish) for malignant breast cancer.
(because enlarge or swollen veins around them
resembled the limbs of
crab).
• The term cancer was translated from a Latin word
carcino i.e. Crab by celsus.
• Galen used ‘oncos’ to describe all tumors, the root
of the modern word ‘oncology’.
9. Significant weight loss
Severe pains
Change in appearance
Blood in vomtings
Chronic cough(lung cancer)
Bowel changes(colon cancer)
Fever(leukemia & lymphoma)
Physical examination
Biopsy
Blood test
Newer molecular & cellular diagnosis
11. 5 MAJOR TYPES
There are five broad groups that are used to classify
cancer.
Carcinomas are characterized by cells that cover internal
and external parts of the body such as lung, breast, and
colon cancer.
Sarcomas are characterized by cells that are located in
bone, cartilage, fat, connective tissue, muscle, and other
supportive tissues.
Lymphomas are cancers that begin in the lymph nodes and
immune system tissues.
Leukemias are cancers that begin in the bone marrow and
often accumulate in the bloodstream.
12. • According to Guinness World Records, the biggest tumor
ever removed intact from the human body weighed in
at 303 pounds (137.6 kg)and measured
• 3 feet (1 m) in diameter.
• The tumor, located on the right ovary, was removed in
1991 during an operation performed by Professor
Katherine O’Hanlan at Stanford University
Medical Center in California.
13. China’s elephant man grows world’s
Largest tumor on face.
(50 pounds)
The man-with-no-face.
15. • The doubling time is the mean (“average”) interval
between successive mitoses.
• It is a characteristic of the particular type of tumor cell.
Doubling time varies markedly among various kinds of
tumors.
• Burkitt’s tumor = it is approximately 24 hours.
• In acute leukemia = 2 weeks.
• In breast cancer = 3 months.
• In multiple myeloma = 6 to 12 months.
• A tumor cell becomes detectable when the number of
cells reaches about 109
to 10 10
cells. This requires 30 to
33 doubling times.
• The neoplasm becomes lethal when the population
reaches about 5x1011
to 5x1012
cells, after 39 to 42
16. GENE CONTOLING CELL CYCLE
•The principle difference between mature of normal tissue and
tumors is …
•The rate of cell replication i.e. proliferation for most normal
tissues equals the rate of cell death (a balance is maintained
between cell renewal and cell apoptosis (programmed cell
death), where as in neoplasm proliferation exceeds the cell
death.
17. Occasionally due to carcinogens (cancer causing agents) one of the
Cell get mutated and does not respond to normal growth control
mechanisms.
This mutated cell undergoes further mutations and transforms i.e.
to Converts in to tumor cell which starts proliferating vigorously. This in turn results in a
mass of abnormal cells (tissues) called tumour Or neoplasm.
18.
19. (
As the tumor cell
grows it require a
Steady supply of
aminoacid,
carbohydrates,
oxygen,nucleic
acid bases,and
growth factors.
Vascular endothelial
growth factor,
fibroblast growth
factor
Interacts
with
receptors
stimulate
Leading to the branching
And extention of
Capillaries process known as
ANGIOGENESI
S
Vascular growth factors are present in normal cells these are released when tissue has
been damaged. Angiogeness helps in the repair of injured tissues and is controlled by
Angiogenisis inhibitors( angiostatin and thrombospondin)
Unfortunately this balance is disturbed in tumour growth.
Newly developing endothelial cells
Release protein
stimulates
20. The agents (physical, chemical and biological) which causes cancer are called
carcinogens.
1 Physical agents: Uv and ionizing radiations (x-ray, gamma and alpha and
beta
rays cause cancer, uv rays of sunlight, nuclear fission. These radiations
have
mutagenic effect.
Ex: Leukaemias, skin, lung, breast, osteosarcoma, thyroid cancer.
2. Biological agents:
a. Bacterial agents: peptic ulcers and chronic gastritis and if these are
b. left untreated for a long time leads to gastric cancer.
c. Fungal agents: The fungus Aspergillus flavus releases aflatoxins in stored
21. a. Viral agents: Cervical cancer,Burkitt’s lymphoma,hairy cell
lukaemia,Haepatic carcinoma.
3. Chemical agents: Alkylating agents, The acylating agents,
Polyaromatic hydrocarbons, Aniline, arsenic, Anthracenes,
dimethylsulphate,diepoxybutane,acetyl imidazole, dimethyl
carbamyl chloride.
4. Genetic factors: Genetic inheritance plays a key role in causing
some of the cancers (breast carcinoma,retino blastinoma.
5. Diet and habits: People taking rich in fats, low fibre content and
stored grains.
22.
23. • AntineoplAstic Agents are the drugs which are
used in to management of malignant disease (i.e. cancer)
• Antineoplastic agents are also known as Cytotoxic agents.
cancer is a very difficult disease to treat. This has been
because of lack of reliable diagnostic tests for the early
detection and not having the compounds which will cure
any form of cancer.
• Anticancer drugs used in the treatment of malignant
disease when surgery or radiotherapy is not possible or has
proved ineffective. They are also employed as adjunct to
surgery or Radiotherapy. They are used as the initial
treatment as in laeukaemia.
• Chemotherapy usually involves combinations of drugs
having
different targets or mechanisms of action.Traditional
anticancer
24. 1.chemotherapy----------rapidly dividing cells (cancer as well as
normal cells)
metastasised cancers
leukemia and lymphoma
2. Radiotherapy---------in combination with other therapies
iodine -131----thyroid cancer
iridium-192----breast cancer
3. surgery----------------not metastasized cancers
prostate,breast or testicular cancers
4.Immunotherapy----- immune system made strong to fight
against cancers
5.Hormone therapy---killing cancer cells by altering hormone levels
tamoxifen reduces estrogen levels killing breast cancer
6. Gene therapy------replacing defective genes
25. • How is cancer diagnosed and staged?
• . Physicians use information from symptoms and several other procedures
to diagnose cancer.
This procedure is called a biopsy.
Physicians will analyze your body's sugars, fats, proteins, and DNA at the
molecular level.
For example, cancerous prostate cells release a higher level of a
chemical called PSA (prostate-specific antigen) into the bloodstream
that can be detected by a blood test.
Common tests include Common tests include the following:
Biopsy of the tumor
Blood tests (which look for chemicals such as tumor markers)
Bone marrow biopsy (for lymphoma or leukemia)
Chest x-ray
Complete blood count (CBC)
CT scan
MRI scan (magnetic resonance imaging)
Extracting cancer cells and looking at them under a microscope is the only
absolute way to diagnose cancer.
26. According to WHO
10 Million deaths worldwide
in 2010
This year till now 7 million
Deaths and 12 million new
cases
According to WHO
10 Million deaths worldwide
in 2010
This year till now 7 million
Deaths and 12 million new
cases
STATISTICS
27. TREATMENT OF CANCER• Cancer can be treated by the following means:
• 1. Surgery
Robotic radical prostatectomy for prostate cancer.
(3-D) view of the surgical field, at a greatly
increased magnification, up to 15 times greater than the human eye.
2. Radiation therapy.
• 3.Immunotherapy.
• 4.Hormonal therapy.
• 5.Antibiotics.
• 6.Chemotherapy.
Chemotherapy is the term applied for a wide range of chemical
substances i.e. drugs that are employed in the treating the cancer.
These drugs may act by various mechanisms like
Interfering with the replication of DNA.
Inhibiting the formation of important molecules which are needed for
DNA formation and inhibiting the mytotic spindle.
31. Alkylating agentsAlkylating agents ::
1.Mustard drugs1.Mustard drugs: Mechlorethamine,: Mechlorethamine, Chlo ram bucil,Chlo ram bucil, Cyclo pho spho m ide ,Cyclo pho spho m ide ,
Me lphalanMe lphalan Nitrogen mustards get their name because they are related to th
sulfur-containing mustard gases used during First world War.
cyclophosphomide
Launcher
CH3
Missile
(odour resembling mustard,garlic plant hence the name given)
32. Alkylating agents
Contains ractive alkyl Groups.
These compounds undergoes
neibhobouring group reactions,
Produce highly reactive
Carbonium ion intermeadiates
Which form covalent bonds
By alkylation at 7th
Position of
guanine in each of The double
starnds of DNA Causing cross
linking/mispairing.
This interferes in the separation
of strands and prevents mitosis or
arrest cell replication.
Alkylating agentsAlkylating agents
Mechanism of action
Alkylation is defined as replacement of hydrogen on an atom by an
alkyl group.
nu - H + alkyl-Y ---------- nu-alkyl + H+
+ Y
-
33. Undergoes neibhobouring group reactions to
form Stained 3 membered onium , ethylene
imminium ion or
Aziridinium ions,which react with guanine
groups on DNA To produce cross-linking.
If second alkyl halide reacts with
Water Cross linking is the major factor
34. CELL CYCLE SPECIFIC AND CELL CYCLE NON SPECIFIC
DRUGS
CELL CYCLE SPECIFIC AND CELL CYCLE NON SPECIFIC
DRUGS
CCS drugs are effective for high growth fraction
malignancies
where as
CCNS drugs for both low and high growth fraction
malignancies.
35. AdversereactIonAdversereactIon
Chemotherapeutic agents damage the
tissues that are having growth fraction, theses
include cancers and also normal tissues such as
bone marrow ,hair follicles, GI tract mucosa ,gonads
etc as a result of action on these tissues the
following adverse actions are commonly seen..
1. bone marrow toxicity
2. impaired wound healing
3. alopecia
4. damage to gastrointestinal
epithelium
5. sterility
6. growth retardment in children
7. teratogenecity.
8. nausea, vomiting and diarrhoea
36. RESISTTANC
EMechanism Drugs or Drug Groups
Change in sensitivity (or ↑ level) or ↓
binding affinity of target enzymes or
receptors
Etoposide, methotrexate, vinca alkaloids,
estrogen & androgen receptors
Decreased drug accumulation via ↑
expression of glycoprotein transporters,
or ↓ permeability
Methotrexate, alkylating agents,
dactinomycin
Formation of drug-inactivating enzymes Purine & pyrimidine antimetabolites
Production of reactive chemicals that
“trap” the anticancer drug
Alkylators, bleomycin, cisplatin.
doxorubicin
Increased nucleic acid repair mechanisms Alkylating agents, cisplatin
Reduced activation of pro-drugs Purine & pyrimidine antimetabolites
37. Chlorambucil
Uses: Multiple myeloma, Lymphosarcoma,Lymphocytic leukemia, Polycythemiavera
Overian adenocarcinoma, Hodkin’s disease and in combination testicular
cancer.
Chlorambucil acts by cross linking of DNA which results in formation of altered
proteins leading to decrease in cell division that ultimately causes death of the cell.
Malignant lymphomas.
38. synthesisSynthesis of 5-
flurouracil
Fluoroxy trifluoro methane
It is a solid, white, odourless, partially soluble in water,methanol, insoluble in diehtyl ether
Having melting point 282o
C.
Adverse /Toxic effects:
Nausea, tiredness, diarrhoea, pigmentation of skin,mouth sores, anaemia.blurred vision
Loss of appetite, rashes, hair thinning , dermatitis.
Therapeutic uses
5-Flurouracil is used for treating the following cancers
Breast cancer
Liver
Skin cancer
Stomach, pancreatic cancer, colon and rectal cancer.
Cancer of anus, bladder, cervix, endometrium, prostrate, ovaries, penis.
5-
39. WIDELY USED DRUGS
Generic Name Brands
®
Companies Indications Sales $ billion
2006 2007 2008
P
A
Rituximab Rituxan Roche NHL, RA 4.7 5.01
5.6
Trastuzumab Herceptin Roche Breast Cancer 3.14 4.4 4.8
Bevacizumab Avastin Roche Colon Cancer 2.4 3.93 4.7
Imatinib
Gleevec
Glivec
Novartis
CML, GIST Chronic Myelogenous Leukemia,
GI Stromal Tumors
2.5 3.1 3.4
Darbepoetin Aranesp Amgen Anemia 4.1 4.2 3.3
Docetaxel Taxotere
Sanofi
Aventis
Breast, Lung, Prostate, Gastric cancer 2.2 2.6 3.2
G-CSF Neulasta Amgen Neutropenia 2.6 2.7 3.2
Human
Papilloma Virus
Gardasil Merck Cervical Cancer 1.5 3.0
Erythropoietin
Procrit
Eprex J&J Anemia 3.2 2.9 2.3
Erythropoietin Epogen Amgen Anemia 2.5 2.6 2.3
Anastrozole Arimidex
Astra
Zeneca
Breast Cancer 1.5 1.7 2.0
BMS,
44. •The presence of acetyl group is very essential for vinblastine to
exhibit it Anti cancer activity. When this is hydrolysed activity
gets destroyed.
2. When free hydroxyl grops were acetylated the drug lost its
Antimalignant activity.
3.The potency of vinblastine reduces drastically when the double
bonds were initially hydrogenated and finally converted to
carbinol group via reduction.
Uses
1.Vinblastine has been used in combination
Therapies for the treatment of lymphomas,
Testicular cancer and ovarian cancer.
Hodgkin’s disease.
45. 1. Campothecin analogs
Camptothecin is an alkaloid which was isolated from
Camptotheca acuminata, used mainly for treating sarcoma and
leukemia.
Why research is going on?
a) Has potent anti tumor activity but has serious
problems with solubility and toxicity.
.
b) very impressive biological activity.
c) The target for development starts with IRINOTECAN which was
recently approved by FDA for treatment of refractory colorectal cancer
d) The aim for the developments is to synthesis water soluble
derivatives of 7-Ethyl-10-Hydroxy Camptothecin.
46. Smokers who smoke between 1 and 14 cigarettes a day have eight times the risk of
dying from lung cancer compared to non-smokers. Smokers who smoke more than 25
cigarettes a day have 25 times this risk compared to non-smokers
facts
You can see how the lung looks
without the effects of inhalation of
smoke.
Note black specks throughout
indicative of carbon deposits from
pollution.
Smokers lung with cancer. White area
on top is the cancer, this is what killed
the person. The blackened area is just
the deposit of tars that all smokers
paint into their lungs with every puff
they take.
47. ALTERNATIVES FOR ANTINEOPLASTICS
Cancer chemotherapy is now entering a new era
Progress in this era has arisen from a better
understanding of the cellular chemistry involved in
particular cancer cells
The use of antibodies and gene therapy is another
area of research which shows huge potential.
48. Finally, one of the best ways of reducing
cancer is …..
• Firstly…Public education campaigns ---30% of cancers are caused by smoking,
excessive drinking, and hazardous solvents
• Secondly, another 30% of cancers are diet related,The benefits of eating high-
fibre foods, fruit, and vegetables are clear
• various research projects aimed at identifying the specific chemicals in these
foods which are responsible for this protective property. For example,
Dithiolthiones are a group of chemicals in broccoli, cauliflower, and cabbage
one of which involves the activation of enzymes in the liver to detoxify
carcinogens
• Genistein is a protective compound found in soy products
• Asian populations have a low incidence of breast, prostate, colon cancers.
• antioxidant present in green tea
• Synthetic drugs are possible cancer preventives
(finasteride, aspirin, ibuprofen, and difluoromethylornithine).
49. Anticancer agents are having severe adverse
effects and their usage should be limited and it
is highly impossible to lead a happy life with
cancer , The only best thing we can do is to
maintain a distance from carcinogens.
50.
51.
52. References
1. Wikipedia
2. William o.foye, textbook of medicinal chemistry
3. 4. Text book of medicinal chemistry by ashutosh kar
5. Text of pharmacology by rang and dale
6. Text book of pharmacology by katsung
7. Text book of biochemistry by rambabu
53. References
• Wikipedia
• William o.foye, textbook of medicinal
chemistry
• Wilson and gisvold`s text book of organic
medicinal chemistry and pharmaceutical
chemistry
• Text book of medicinal chemistry by ashutosh
kar
• Text of pharmacology by rang and dale.
• J.med.chem.,1996,39,3806-3813
• EP-236940.
• 10. J.org.chem.,46(5)846-851,1981.
• J.Am.chem.soc.,48,2379(1926)
• Chem.pharm.bull.,39,6-1446-1454(1991)