This presentation on Cancer contains description of cancer, its types, causes, treatment options and useful herbs.

1. CANCER
CANCER
A PRESENTATION BY SURYA PRAJAPAT
SURYA

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CONTENTS
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What is caner?
Types of cancer
Origin of cancer
Pathophysiology
Carcinogenesis
Causes of Cancer
Treatment
Herbs used in treatment of cancer
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What is cancer?
• Cancer is medically called Malignant Neoplasm.
It involves unregulated cell growth.
In cancer, cells grow continuously and uncontrollably which
forms malignant tumors and invade nearby parts of the body.
Cancer generally spreads through lymphatic system or blood
stream.
There are several types of cancer depending on the organ they
effect. They possess same common properties of:
1. Abnormal cell growth
2. Capacity to invade other tissues
3. Capacity to spread to distant organs via blood or lymph.
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• The body is made up of trillions of living cells. These cells grow
divide and die in an orderly fashion. This process is regulated
and controlled by DNA. In an adult person most cells divide to
replace the damaged or dying cells or to repair tissues injuries.
• When cells at particular site starts to grow out of control, they
may become cancerous. Cancer cell growth is different from
normal cell growth. Instead of dying, cancer cells continue to
grow and form new abnormal cells.
• Tumor- Any abnormal swelling, lump or mass inside body.
• Neoplasm – Scientific term to describe abnormal proliferation
of genetically altered cells.
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• Types of cancer or tumor
Tumor
Malignant Tumor
In Malignant Tumor cells
grow uncontrollably and
invade neighboring tissues.
It is Cancerous and are
usually named using
-carcinoma, -sarcoma,
-blastoma as a suffix
Eg- Liver : hepatocarcinoma
Breast cancer : mammary
ductal carcinoma
Benign Tumor
In Benign Tumor cells do not grow
uncontrollably and do not invade
neighboring tissues.
It is Non cancerous and can be
removed.
Benign tumors are named using
-oma as suffix with the organ
name as the root.
Eg- BT of uterus smooth muscle:
Leiomyoma
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• Some cancer do not form tumors.
Eg: Leukemia – cancer of blood and bone marrow.
• Local symptoms may occur due to the mass of the tumor or its
ulceration.
Eg: Lung cancer : blockage of bronchus resulting in cough &
pneumonia.
Esophageal cancer: narrowing of esophagus and difficult
to swallow.
Colorectal cancer : narrowing or blockage in bowel.
• Tumor with ulceration can cause bleeding which if it occurs in
lungs will lead to coughing up blood.
Blood in bowel causes anemia
Blood in bladder leads to urine with blood
Blood in uterus causes vaginal bleeding
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• Other types of cancer:
1) Carcinoma : cancer that begins in the skin or tissue that
covers internal organs.
eg: Adenocarcinoma – a malignant epithelial tumor arising
from glandular structure which are constituent parts of most
organs of the body.
Esophageal cancer, Colorectal cancer.
2) Sarcoma: cancer that begins in bone, cartilage, fat, muscles,
Blood vessels or other connective or supportive tissue.
3) Leukemia : cancer that starts in blood forming tissues like
bone marrow and causes large number of abnormal blood
cells to be produced and enter the blood.
4) Lymphoma & myeloma : cancer that begins in the cells of
immune system.
5) CNS cancer : cancer that begins in the tissues of brain and
spinal cord.
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6) Germ cell tumor : tumor derived from totipotent cells. In
adults most often found in testes & ovary. In children
it is found in tip of tailbone
7) Blastic tumor/ Blastoma : a tumor which resembles an
immature or embryonic tissue.
Metastasis : The distant spread of malignant tumor from its site
of origin by three routes blood lymph and body cavities.
Eg : carcinoma- via lymphatic
sarcoma – via blood stream
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• Origin of cancer
All cancer begins in cells, the body’s basic unit of life.
The body is made up of many types of cells. These cells grow
and divide in a controlled way to produce more cells to keep
the body healthy. When cells become old and damage they
die and replaced by new ones.
But sometimes this orderly process goes wrong. Genetic
material i.e DNA of cell is changed or damaged due to which
normal cell growth and division change, as a result mutation
takes place. Hence cells do not die when required and new
cells form when body not needed. These extra cells form mass
of tissue called tumor.
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• Flow chart representation
Genetic Material – DNA of cells damage/change
Normal cell growth and division change
Mutation occurs
Cells do not die when required and new cells form
when not needed
These extra cells form mass of tissue called tumor
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• Flow chart representation :
Genetic Material – DNA of cells damage/change
Normal cell growth and division change
Mutation occurs
Cells do not die when required and new cells form
when not needed.
These extra cells form mass of tissue called tumor
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Pathophysiology
Genetic alteration- Cancer is the disease of failure of tissue growth
regulation. Gene which regulate the cell growth and differentiation
when altered, then normal cell transform to a cancer cell.
Oncogene- are the genes which promote cell growth and
reproduction.
Tumor suppressor genes- are the genes which inhibit cell division
and survival.
Inappropriate overexpression of normal oncogenes/under
expression or disabling of tumor suppressor gene causes Malignant
transformation.
Genetic changes can occur through mutation i.e change in
nucleotide sequence of genomic DNA, which causes gain or loss of
entire chromosome through errors in mitosis.
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• DNA virus or retrovirus cause integration of genomic material which
can result in disruption of a single gene.
• Replication of enormous data contained within DNA of living cells
result in some errors.
• If significant error occurs, the damaged cell can self destruct
through programmed cell death called Apoptosis.
• if the error control process fails then the mutation will survive and
be passed along to daughter cells.
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• Carcinogenesis
Carcinogenesis is also called Oncogenesis or tumorigenesis.
It is a process by which normal cells are transformed into cancer
cells.
Cell division is a physiological process which maintain balance
between proliferation and programmed cell death in form of
apoptosis.
Carcinogenesis is caused by mutation and epimutation of
genetic material of normal cells, which upsets the normal
balance between proliferation and cell death.
More than one mutation to certain classes of gene are required
for carcinogenesis.
Large scale mutation : it involves gain or deletion of a portion of
chromosome. Genomic duplication occurs when a cell gains
many copies of a small chromosomal region containing one
or more oncogenes and genetic material.
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Translocation occurs when 2 separate chromosomal regions
become abnormally fused.
Eg: translocation of chromosome 9 & 22 occurs in chronic
myelogenous leukemia and results in production of protein
called tyrosine kinase.
Small scale mutation : it include point mutation, deletion and
insertion which occurs in promoter of a gene and affect its
expression and alter the function of protein product.
Epimutation : it include methylation or demethylation of the
CpG islands of the promoter regions of genes which results in
repression or de-repression of gene expression.
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Causes of cancer :
90-95% is due to Enviornment causes.
5-10 % is due to Genetic causes.
Enviornmental causes include: tobacco – 25-30%
Diet & obesity – 30-35%
Infection – 15-20%
Radiations – 10%
Stress & lack of physical activity
1) Tobacco & cancer – Tobacco smoking is associated with
many forms of cancer and causes 90% of lung cancer.
It causes cancer in lungs, larynx, stomach, head , neck,
bladder, kidney, esophagus, pancreas. Tobacco smoking
contains 50 known carcinogens including nitrosamines and
polycyclic aromatic hydrocarbons.
2) Diet and exercise – Diet, physical inactivity and obesity are
related to 30-35% of cancer deaths.
90
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Diet that are low in vegetables, fruits and whole grains or high in
red meat are linked with cancer.
Eg: High salt diet – Gastric cancer
Betel nut chewing – oral cancer
3) Infection – A virus that can cause cancer is called oncovirus.
Eg: Viral infection cancer:
Human papilloma virus- cervical carcinoma
Epstein-Barrvirus – B cell lymphoproliferative disease
Nasopharyngeal carcinoma
Kaposis sarcoma herpesvirus – Kaposi’s sarcoma: a
malignant tumor arising from blood vessel in the
skin and appear as purple plaques or nodules.
Hepatitis B and C virus – Hepatocellular carcinoma
Human T cell leukemia virus 1 – T cell leukemias.
Eg: Bacterial: Helicobacter pylori- Gastric carcinoma
Eg: Parasitic : Clonorchis sinensis – MT of bile ducts.
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4) Radiations : causative radiations are both ionizing and nonionizing UV radiations.
Sources of radiations – Medical imaging, Radon gas.
Mechanism of Action:
Ionizing radiations hit chromosomes
abnormal no. of chromosomes
chromosomes translocation
occur
Major damage
cell die
Small damage
cell partially functional,
proliferate abnormally
Develop cancer
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Non ionising radiations – UV rays, mobile radiations.
Radon : A radioactive gas released from normal decay of
elements like uranium, thorium and radium in rocks, soil.
Radon decay quickly giving off cancerous radioactive
particles.
5) Physical agents : Asbestos causes mesothelioma: tumor of
pleura, peritonium or pericardium.
other elements are cobalt, nickel,
crystalline silica, hair dyes, formaldehyde.
6) Hormones : Increase in sex hormones(contraceptives,
menopausal hormones) can cause cancer.
Diethylstylbesterol – synthetic form of estrogen which can
cause breast cancer if taken during pregnancy.
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TREATMENT
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3.
4.
5.
6.
7.
Surgery
Radiation Therapy
Chemotherapy
Targeted Therapy
Immunotherapy
Hormonal Therapy
Angiogenesis Inhibitor
1. SURGERY – Non haematological cancer can be cured if entirely
removed by surgery. But if cancer has already spread to other
sites in the body i.e Metastasis, then removing all cancer by
surgery is not possible.
Initially cancer grows locally and then spread to lymph nodes
and then to rest of the body. So for small cancer surgery
became popular treatment.
Eg : for Breast cancer – Mastectomy surgery
for prostate cancer - prostatectomy
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Goal of surgery is the removal of only tumor or removal of entire
organ.
Surgery is often necessary for staging also. (Staging means
determining the extent of disease whether metastasized to lymph
nodes.)
Drawback – sometimes when any single cancer cell is left, it can
grow and cause cancer again called recurrence.
2) RADIATION THERAPY – also called Radiotherapy.
• It is the medical use of Ionizing Radiation as a part of cancer
treatment to control malignant cells.
• Radiotherapy is used for curative therapy or adjuvant cancer
treatment or palliative treatment (where cure is not possible and
aim is to control disease or provide symptomatic relief).
• Total Body Irradiation (TBI) is a radiotherapy technique used to
prepare the body to receive bone marrow transplant.
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• MOA of RadiotherapyRadiotherapy works by damaging the DNA.
Photon, electron, proton, neutron or ion beam directly or indirectly
ionize the atoms which make up the DNA chain.
Indirect ionization happens as a result of ionization of water
to form free radicals (hydroxyl radicals)
DNA damage.
Breaking the DNA on both strands is necessary because cells have
mechanism to repair DNA damage.
DNA damage is inherited to cancer cells
Damage accumulate to cancer cells
Cancer cell die or reproduce more slowly
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Uses – 1) In malignant tumor as primary therapy.
2) In non-malignant conditions as –
•
Trigeminal neuralgia : brief paroxysms of searing pain felt in
the distribution of trigeminal nerve branches in the face.
•
Severe thyroid eye disease
•
Pterygium : a triangular overgrowth of the cornea.
•
Pigmented villonodular synovitis : inflammation of
synovium membrane that lines the joint capsule.
•
Prevention of keloid scar growth : an overgrowth of fibrous
scar tissue following trauma to the skin.
•
Prevention of heterotopic ossification (osteogenesis).
•
Radiotherapy is commonly combined with surgery,
chemotherapy, hormone therapy.
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CANCER
Major Limitation : cells of solid tumor become more deficient in oxygen
because solid tumor usually outgrow their blood supply and cause a low
oxygen state called Hypoxia.
More hypoxia the tumor more resistant to radiation because oxygen
makes the radiation damage to DNA permanently.
Side effects : (a) Acute - Damage to epithelial surface, swelling, edema,
infertility(no gametes formation), generalized fatigue.
(b) Long term – fibrosis, hair loss, dryness, fatigue, cancer.
Dose : The amount of radiation is measured in Gray (Gy)
Curative dose – solid epithelial tumor : 60 to 80 Gy
lymphoma tumor
: 80 to 100 Gy
Preventive dose – Breast, head & neck cancer : 45 to 60 Gy in 1.8 to 2 Gy
fractions.
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• Types of Radiation Therapy :
Three main divisions of radiotherapy are –
1. External Beam Radiotherapy (EBRT/ XBRT) or Teletherapy.
2. Brachytherapy or sealed source radiotherapy.
3. Unsealed source radiotherapy.
EBRT is the radiotherapy given outside the body.
Sealed & unsealed – radioactive material delivered inside the body.
Conventional External Beam Radiotherapy : 2DXRT is delivered via 2
dimensional beams using linear accelerator machines.
Virtual simulation, 3-D conformal radiotherapy & intensity modulated
radiotherapy – this radiotherapy delineate tumors in 3-D using CT or
MRI scan.
Radioisotope therapy (RIT) – Radiotherapy can be delivered through
infusion (in blood stream) or ingestion also.
Eg: For neuroblastoma - infusion of metaiodobenzyl guanidine.
For thyroid cancer – infusion of oral iodine-131
For neuroendocrine tumors – infusion of Lutetium-177
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3) CHEMOTHERAPY –
chemotherapy means use of chemical agents to destroy cancer cells.
It has the ability to treat widespread and metastatic cancer. While
radiotherapy and surgery are confined to specific areas only.
How do chemotherapeutic drugs work?
For chemotherapeutic agents the potential target is cancer cell, which
should be differentiated from normal tissues. Hence the
differentiation evolved was that cancer cells grow at a rate faster
than normal cells.
Therefore the conclusion came was that cell growth cycle should be the
target for chemotherapeutic drugs. Fast growing cells would be
affected the most while slow growing the least. This is the basis of
many chemotherapeutic agents. Looking towards the side effects
hair follicles, skin, gastrointestinal lining cells are also affected as
they are the fast growing cells.
Administering the recommended amt. of drugs(chemo) may prove to
be too toxic to metabolize & excrete. So patients with kidney or
liver damage are given chemo on precautions.
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• Cell cycle- cell cycle is the sequence of steps a cell goes through in
order to copy its genetic material and divide into 2 cells.
The cell cycle is divided into 4 phases – G1 S G2 M
A chemotherapeutic agent may be –
cell cycle specific: acts in only one phase of the cycle.
cell cycle nonspecific: acts in all phases of cell cycle.
G1 phase : most active in protein synthesis. Cellular DNA is tightly coiled
and is not actively being transcribed (copied).
S phase : is the synthetic phase of cell cycle. DNA replication is most
active in this phase.
G2 phase : when mostly RNA is actively produced.
M phase : mitosis/cell division occur in this phase.
So by knowing the phase an agent works in, we are able to combine
agents that work in different phases to achieve most tumor killing.
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28. • Chemotherapeutic drugs (classification) :
(a) Cytotoxic drugs (drugs acting directly on cells) – alkylating agents,
Ethylenimine, Alkyl sulfonate, nitrosoureas, triazines.
(b) Antimetabolites – Folate antagonist, purine antagonist, pyrimidine
antagonist.
(c) Vinca alkaloids
(d) Taxanes
(e) Epidophyllotoxins
(f) Camptothecin analogue
(g) Antibiotics
(h) Miscelleneous
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CANCER
Alkylating agents : are nitrogen mustard & cell cycle non specific.
Binds to –ve charged sites on DNA like oxygen, nitrogen, ph, sulphur
so that steps of cell duplication(transcription, replication, base
pairing) are altered. Also alkylating agents cause alkylation of DNA
& DNA strands break. Cellular activity stops and cell dies.
Risks- sperm production ↓, menstruation cease, permanent infertility.
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• Antimetabolite : They completely inhibit utilization of the normal
substrate or get themselves incorporated to form dysfunctional
macromolecule.
Eg: methotrexate : is cell cyle specific and kills cells in S-phase,
primarily inhibits DNA synthesis but also affects RNA & protein
synthesis.
Risks- megaloblastic anemia, pancytopenia( ↓ in WBC, RBC, Platelets)
• Purine Antagonist : inhibits the formation of adenine & guanine
nucleotides. Eg: mercaptopurine(6-MP), Thioguanine (6-TG)
• Pyrimidine antagonist : Eg: Methotrexate
Deoxyuridilic acid
Methotrexate
-thymidylate synthase
deoxythymidylic acid
So in the absence of deoxythymidylic acid DNA synthesis fails.
• Camptothecin analogue : binds to DNA topoisomerase I, so DNA
strand breaks. Acts in S-phase and arrest cell cycle in G2 phase.
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• Vinca alkaloid : are mitotic inhibitors.
Binds to tubulin protein & prevent the assembly of microtubules.
Cause disruption of mitotic spindle
Chromosomes fail to move apart during mitosis
Metaphase arrest occur.
Eg: Vincristine- used in:
Lymphosarcoma : a malignant tumor of lymph nodes.
Hodgkin’s disease : form of lymphoma characterised by painless
enlargement of one or more groups of lymph nodes in neck, axillae,
groin, chest, abdomen.
Ewing’s sarcoma: a malignant tumor of bone.
Vinblastin – used in Hodgkin’s disease and testicular sarcoma.
• Taxanes : same as Vinca alkaloids.
Eg: paclitaxel
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Chemotherapy administration : most common routes are mouth, vein, muscle.
Chemotherapy can be administered directly in a specific cavity i.e
intracavitary, in abdomen- intraperitoneal, in lung – intrapeural,
in CNS- intrathecal.
Additional pretreatment actions such as increased IV fluids or administration
of antinausea medicinesare needed to decrease the side effect.
4) TARGETED THERAPY : it refers to a medication that targets a specific
pathway in the growth and development of tumor. The target themselves
are typically various molecules in the body known to play role in cancer
formation.
Types- 1) Tyrosine kinase inhibitor – it is a receptor which when blocked
prevents the cascade of reaction and prevent tumor survival.
2) Angiogenesis inhibitor – like normal cells tumor cells also need blood
supply to perform vital cellular functions. Inhibiting angiogenesis
(formation of blood vessels) can inhibit the growth of tumor cells.
3) Proteasome inhibitors – proteasome is a structure inside cell which
breaks down the protein which are supposed to degrade & recycle.
Inhibiting this enzyme can arrest the tumor cell growth.
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5) IMMUNOTHERAPY : it does not interfere with growth by binding to target
but it triggers immune signals.
Antigens on cancer cell surface are captured by antibodies (specific) which
leads to antitumor immune reaction. These Ab are monoclonal.
When there is a radioisotope attached these drugs are called
radioimmunotherapy.
Eg : Alemtuzumab – chronic lymphocytic leukemia.
Beracizumab – colon cancer.
6) HORMONAL THERAPY : by administering hormones (steroid), endocrine
system is manipulated and particular hormone activity is inhibited due to
which certain cancer cells cease growing or they die.
It is used in breast cancer, prostate cancer, endometrium cancer, adrenal
cortex cancer.
Inhibitors of hormone synthesis –
a) Aromatase inhibitors – used for breast cancer in postmenopausal women.
At menopause, estrogen production in ovaries stops, but other organs
continue to produce estrogen by the help of aromatase.
Aromatase action inhibited
estrogen level ↓
apoptosis of hormone
responsive cancer cell.
Eg : Letrozole, anastrozole.
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b) GnRH analogue – Gonadotropin releasing hormone analogue can be
used to induce a complete castration i.e complete suppression of
estrogen & progesterone from ovaries and testosterone production
from male testes.
Eg : leuprolide, goserelin
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• Herbs used in the treatment of cancer :
• Plants derived 9 compounds contain anticancer properties
1. Vinblastin
2. Vincristine
3. Etoposide
4. Teniposide
5. Taxol
6. Navelbine
7. Taxotere
8. Topotecan
9. Irinotecan
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1. Vinblastin & Vincristine : are vinca alkaloids
obtained from Catharanthus Rosea of Apocynaceae family.
Also called Madagascar periwinkle.
It is an antimicrotubule drug used to treat certain kinds of cancer like
hodgkin’s disease, non small cell lung cancer, Head & Neck cancer, breast
cancer, Testicular cancer.
Vinblastin is a chemical analogue of Vincristine. It binds to tubuline
protein : is a structural protein which polymerizes to microtubules.
Vinblastin
Tubulin -- assembly of microtubule
M-phase arrest
Mitosis
inhibited
seperation of chromosomes
during anaphase not occur
Side effects : hair loss,
loss of WBC & platelets,
GI problem, high BP,
vertigo
muscle cramp.
proper spindle not
form
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2) Etoposide : Synthesized from podophyllotoxin : a toxin found in
Podophyllum peltatum (American Mayapple)
It is a cytotoxic agent (anticancer drug) and belongs to drug type
topoisomerase inhibitors.
(Note- rhizome, foliage and roots of this plant are poisonous.)
MOA- etoposide blocks the action of topoisomerase II. Cells need this
enzyme to keep their DNA in proper shape when they are dividing in 2
cells. As a result DNA break and cell death occur
Uses : Kaposi’s cancer
Ewing’s cancer
Lung cancer
Testicular cancer
Lymphoma
Non lymphocytic leukemia
Side effects : low BP, hair loss, pain & burning at IV sites, constipation,
metallic food taste, bone marrow suppression, anemia, platelets & WBC
decrease.
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3) Teniposide (vumon, VM-26): is a chemotherapeutic medication.
Mainly used in the treatment of childhood Acute lymphocytic
leukemia.
It is a podophyllotoxin derivative which slows down the growth of
cancer cells.
MOA: it inhibits the enzyme topoisomerase II and thus break DNA
strands, cell death occur.
It is administered by injection in vein.
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3) Taxol : generic name is paclitaxel.
Taxols are anticancer drug of taxanes which are made from the bark
of Pacific yew tree (taxus brevifolia).
Taxol is a mitotic inhibitor. It is a antimicrotubule agent which inhibit the
microtubule structures within the cell. Microtubule are the part of cell’s
apparatus for dividing and replicating itself.
Paclitaxel is a cytoskeletal drugs that target tubulin.
MOA : Unlike other tubulin targeting drugs, that inhibit microtubule
assembly, paclitaxel stabilizes the microtubule polymer and protects it
from disassembly
Chromosomes unable to achieve metaphase
spindle configuration
Apoptosis occur/ reversion
mitosis progression
of G-phase of cell cycle take
inhibited
place without cell division
Note : microtubule assembly and disassembly both are essential for cell
division, if any one is inhibited cell division inhibits.
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Uses : Paclitaxel is approved in UK for 1st and 2nd line treatment of
ovarian cancer. Also used in breast cancer, lung cancer and Kaposi’s
sarcoma. NICE (National Institute of Health and Care Excellence)
recommended paclitaxel not to be used in the adjuvant treatment of
early node-positive breast cancer.
4) Navelbine : is a semisynthetic vinca alkaloid obtained from
catharanthus roseus. It is an antimicrotubule agent available in IV
injection form. It inhibits the mitosis at metaphase.
5) Taxotere (Docetaxel): is antimitotic chemotherapy medication.
Taxotere is used for the treatment of breast, ovarian, prostate and
non-small cell lung cancer who have undergone anthracycline
based chemotherapy and failed to stop cancer progression.
MOA – it binds to microtubule and stabilizes and prevents
depolymerization of microtubule, as a result there is decrease in
the free tubulin needed for microtubulin formation and cell
division inhibited.
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Because microtubule do not assembly in presence of docetaxel, they
accumulate inside the cell and cause apoptosis initiation.
Uses : in Breast cancer, colorectal, lung, ovarian, prostate, liver, renal,
gastric, head & neck cancer.
6) Topotecan (Hycanitin): it is water soluble derivative of camptothecin
and is topoisomerase inhibitor.
camptothecin is a natural product extracted from the bark of tree
called Camptotheca accuminata.
Topoisomerase I is a nuclear enzyme that relieves torsional strain in
DNA by single strand break. Topotecan intercalates between DNA
and bases. This intercalation disrupts the DNA duplication and
cause cell death.
Uses : ovarian, cervical and small cell lung cancer.
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Thank You
A PRESENTATION BY SURYA PRAJAPAT
SURYA