ANTINEOPLASTIC AGENTS
Edited by:
Israa Eltayib
Antineoplastic Agents
Antineoplastic medications:
drugs used to treat cancer,
also called cancer drugs
,cytotoxic agents and
anticancer drugs.
Problems associated with chemotherapy
1-Resistance to chemotherapy
• Resistance to chemotherapy may develop by several
mechanisms:
1. Decrease in the amount of drug uptake by cancer cells
e.g, Methotrexate
2. Increase in the amount of drug removed by cancer
cells. (Transporters=P-glycoprotein). e.g, Vinblastine
,doxorubicin, bleomycin ,etapsoid….
3. Decrease or alteration in target molecule sensitivity –
this is caused by mutation in the molecule targeted by
the drug e.g, Methotrexate, Mercaptopurine,
doxorubicin
4. Increase in DNA repair ability of the cell via an
increased expression of DNA repairing enzymes. e.g,
Alkylating agent
2-Toxicity and side Effects of Antineoplastic
Agents:
• Normal cells in the body that tend to be
injured by the chemotherapy are those
which have a high growth fraction.
• They are bone marrow, GI Tract ,hair
follicles, reproductive organs .
• Leading to the followings:
– Alopecia- hair loss
– Myelosuppression-bone marrow loss
– Emetic potential: disruptive to cells in
stomach which causes: Nausea/vomiting
– Low WBC count- low immunity
Treatment of Chemotherapy Toxicity
Injury to:
Results in:
Time Course:
Treatment of this side
effect:
Other:
Bone marrow:
Decreased
Neutrophils
Infection
Begins 10-14 days after
tmt initiation. Takes 3-4
wks for recovery.
Give colony stimulating
factors (CSFs)
.
Bone marrow:
Decreased Platelets
Bleeding, especially
from nose and gums
Bone marrow:
Decreased
Erythrocytes
Anemia
GI tract
Stomatitis –(1
inflammation of
mucous lining of
mouth)
pain and infection(2
3)Nausea + vomiting
Hair follicles
Alopecia
Reproductive tract
Irreversible sterility in
males, teratogenic
Platelet infusion
120 days after therapy is
imitated. By this time
therapy has usually
stopped, so this is a rare
effect.
is
an
essential hormone for red
Begins a few days after
tmt initiation and lasts
until two weeks after
termination of tmt.
Treat stomatitis with
anesthetics and antifungal.
Treat nausea with antiemetics like ondansetron
Begins 7 –10 days after
initiation of tmt and
continues until 1 – 2
months post tmt.
)*Erythropoietin
cell production.
...
Erythropoetin
reversable
You can also use
glucocorticoids&
lorazepam to reduce the
inflammation.
3-Treatment-induced tumor
• Many anticancer drugs are mutagens and
can cause the rise of neoplasm ten or more
years after the original cancer was cured.
Cell cycle
Scientists have determined that cell
cycle can be divided into:.
Gap 0 (G0): There are times when a cell
will leave the cycle and quit dividing.
This may be a temporary resting
period or more permanent. An
example of the latter is a cell that has
reached
an
end
stage
of
development and will no longer
divide (e.g. neuron).
Gap 1 (G1): Cells increase in size in Gap
1, produce enzymes needed for DNA
synthesis
S Phase: To produce two similar
daughter cells, the complete DNA
instructions in the cell must be
duplicated. DNA replication occurs
during this S (synthesis) phase.
Gap 2 (G2): It is the gap between DNA
synthesis and mitosis, the cell will
continue to grow and produce new
proteins & RNA.
Mitosis or M Phase: Cell growth
and protein production stop at
this stage in the cell cycle. All
of the cell's energy is focused
on the complex and orderly
division into two similar
daughter cells.
CYTOTOXIC DRUGS
I-Alkylating Agents (CCNS-cellcycle
Non-specific)
Mechanism of Alkylating Agents
• These drugs work by alkylation with nucleophilic substitution . They
alkylate a variety of cellular constituents, such as cell membranes,
proteins, and most importantly DNA.
More specifically, the
nitrogenous bases of DNA are alkylated.
• (*nucleophilic substitution is a fundamental class of reactions in
which an electron nucleophile(Common nucleophiles are hydroxide
ions, cyanide ions, water and ammonia.) selectively bonds with or
attacks the positive or partially positive charge of an atom or a group
of atoms to replace a so-called leaving group; the positive or partially
positive atom is referred to as an electrophile. The whole molecular
entity of which the electrophile and the leaving group are part is
usually called the substrate.)*
•
The drugs start off as pro-drugs that become activated
when a chlorine atom is extracted. A carbonium ion is
thus formed. This “carbonium ion” is very electrophilic
and will then attack any free pair of electrons (i.e. on the
N7 of guanine). This electrophilic attack results in a
bond being formed between the drug and the guanine of
DNA. As a result of this “alkylation”, there are a few
consequences:
1) Miscoding (In transcription)
2) Cross linking- this only occurs if the drug is
bifunctional (*bifunctional, meaning they have two active
sites. Create a carbonium ion that reacts
with
guanine nucleophile. Causes interstrand crosslinking,
which halts replication*).
Alkylating Agents(CCNS)
Subgroups of Alkylating Agents
1)
2)
3)
4)
Nitrogen mustards
Nitrosoureas
Alkyl sulfonates
4-Platinum Coordination Compounds
1-Nitrogen Mustards
E.G.: Mechlorethamine, cyclophosphamid, melphalan & chlorambucil
a-Mechlorethamine
- first alkylating agent employed clinically
- bifunctional, thus can crosslink DNA
- extremely unstable and is inactivated within a few minutes following
administration. Thus it is given IV.
Clinical Uses
-Hodgkin’s Disease (*Hodgkin disease (Hodgkin lymphoma) is a
type of lymphoma, a cancer that starts in cells called
lymphocytes, which are part of the body's immune system.*)
-Non-Hodgkin’s Lymphoma
Toxicity/ Side Effects
- Dose limiting toxicity is bone marrow depression
- Nausea/ Vomiting
- Alopecia
- Diarrhea
- Sterility (*inability to effect
sexual reproduction *)
b-Cyclophsphamid
-It acts as cytotoxic and immunosuppressor agent.
- Prodrug which must be activated by the cytochrome
p450 system, which turns it into a nitrogen mustard.
- bifunctional agent
-most widely used alkylating agent
Clinical Uses
- Hodgkin’s Disease
- Non-Hodgkin’s lymphoma
- Solid tumors of head, neck, ovaries, and breast
- frequently used in combination with methotrexate (antimetabolite) or doxorubicin (anti-tumor antibiotic), or
fluorouracil as adjuvant therapy post breast cancer surgery
- Organ transplant recipients (due to immunosuppressive
actions)
Toxicity/ Side Effects
- bone marrow depression
- severe nausea and vomiting
- acute hemorrhagic cystitis and renal damage??
(can be minimized via high fluid intake/infusion
and the use of………?)
- sterility
- hypersensitivity reactions
Treatment of cyclophsphamid toxicity
2-Nitrosoureas
- bifunctional
- active against broad spectrum of neoplastic
disease
- inhibits synthesis of both DNA and RNA, as well
as proteins
- These drugs are highly lipophilic, so they can
easily cross blood-brain-barrier, and are great for
CNS tumors.
- Big problem in this class is that they are highly
mutagenic and highly carcinogenic.
- Major toxicity is DELAYED bone marrow
depression & Pulmonary fibrosis.
Clinical uses
- primary and metastasis tumors of the brain
- Hodgkin’s Disease
Non-Hodgkin’s lymphoma (*The non-Hodgkin
lymphomas doolb fo puorg esrevid era )sLHN(
tpecxe amohpmyl fo dnik yna edulcni taht srecnac
.samohpmyl s'nikgdoH*)
- Adenocarcinoma of stomach, colon, and rectal
cancer
- Hepatocarcinoma
E.G.:
a-Carmustine
b-Lomustine
3-Alkyl Sulfonates
Busulfan
Clinical uses
Great effect on for Chronic granulocytic Leukemia
Toxicity/ Side Effects
- Dose limiting toxicity is bone marrow depression.
- Pulmonary infiltrates and pulmonary fibrosis
- Tonic-clonic seizures in epileptics
- Nausea and vomiting
- Alopecia
- Sterility (*inability to effect sexual reproduction *)
- Skin hyper pigmentation
- Cataracts
- Hepatitis
4-Platinum Coordination Compounds
E.G.:
Cisplatin
• forms crosslinks within DNA strands. Cis-platin is not really an
“alkylating” agent, but since it operates via the same mechanism
as the alkylating agents, it is placed within that group.
Clinical Uses
- Very powerful against TESTICULAR CANCER
- Also good for carcinomas of ovary, bladder, head, and neck
Toxicity/ Side Effects
- Renal tubular damage (minimized via massive hydration, coupled
with anti-emetics)
- Ototoxicity and peripheral neuropathy
- VERY SEVERE vomiting( Ondanosetron…?)
Carboplatin:
is a derivative of cisplatin with less nephero- ,neuro- &
ototoxicity.(L.E)
Lecture No: 02
II-Antimetabolites (CCS)
An antimetabolite is a chemical with a similar structure to a
metabolite required for normal biochemical reactions, yet
different enough to interfere with the normal functions of
cells, including cell division.
All antimetabolites are used in cancer treatment, as they
interfere with DNA production and therefore cell division and
the growth of tumors (mainly in S-phase specific).
They are classified into:
1- Folic acid analogues
2- Purine analogues
3- Pyrimidine analogues
II-Antimetabolites (CCS)
Purin and pyrimidine antagonists are
phosphorelated inside the body into nucleotid
form in order to be cytotoxic
Uses
leukemia.
non-Hodgkin's lymphoma
inflammatory bowel disease such as Crohn's
Disease and ulcerative colitis
It is widely used as immunosuppressant in
transplantations to control rejection reactions.
1-Folic acid analogues
Methotrexate:
• A folic acid analogue, prevents the formation of
tetrahydrofolate, essential for purine and pyrimidine
synthesis, by inhibiting dihydrofolate reductase. This
leads to inhibition of production of DNA, RNA and
proteins (as tetrahydrofolate is also involved in the
synthesis of amino acids as serine and methionine).
• It is actively taken up into the cells by the same transport
system for folate (resistance…..?)
• The most common toxicity is nepherotoxicity
(precipitation of the drug in renal tubule.)
Cont: Folic acid analogues
1-Methotrexate compete with folic acid for DHFR and inhibits it .
Therefore, it inhibits the synthesis of DNA, RNA and proteins.
2-Also,DHFR catalyses the conversion of dihydrofolate to the
active tetrahydrofolat which is needed for the de novo synthesis
of the deoxynucleoside thymidine phosphate DTMP ( required
for DNA synthesis)
2-Purine analogues
Mercaptopurine (6−mercaptopurine, or 6−MP) :
• It is immunosuppressive cytotoxic substance. It is widely
used in transplantations to control rejection reactions.
• It is acts as a purine analogue and once enter the cell, it is
converted to 6-MP-ribosephophate and can be
incorporated into RNA&DNA resulting in non functioning
RNA & DNA & finally inducing cell cycle arrest and
apoptosis.
-It also inhibits purine ring biosynthesis
Adverse reactions
• Diarrhea, nausea, vomiting, loss of appetite,
• Allergic reaction include rash, itching, swelling, dizziness,
trouble breathing.
• Mercaptopurine cause myelosuppression. Those taking
mercaptopurine should get permission from a doctor in
order to receive immunizations and vaccinations.
Azathioprine:
It is one of the main immunosuppressive
cytotoxic substance. It is widely used in
transplantations to control rejection reactions.
It is nonenzymatically cleaved to 6 - M P that
acts as a purine analogue and inhibits DNA
synthesis
3-Pyrimidine analogues
5-flurouracil (5-FU)
• It act as a uracil analogue, it is transformed inside the cell
into 5-FU deoxynucleotide which compete with
deoxyuridine monophosphate DUMP for thymidylate
synthase leading to inhibition of deoxythymidine
monophosphate DTMP synthesis so inhibition of DNA
synthesis (Not RNA or protein)
• Also it is incorporated into DNA , non functioning DNA .
• finally inducing cell cycle arrest and apoptosis by
inhibiting the cell's ability to synthesize DNA.
• It is an S-phase specific drug
• 5−FU may be used in combination with other
chemotherapy agents to treat cancers of the breast,
stomach, colon, rectum, and pancreas.
Side effect
1- Most unwanted effect is GIT epithelial
damage, diarrhea and mouth ulcers.
2-the most dangerous side effect is bone
marrow suppression
Cytarabine
It is analogue to 2-deoxycytidine and in the
body it is converted into cytosine triphosphate
and inhibit DNA polymerase thus inhibiting DNA
synthesis.
5-flurouracil (5-FU)
Cytarabine
III-Antitumor antibiotics (CCNS) :
1-Dactinomycin
is isolated from soil bacteria of the genus
Streptomyces.
It was the first antibiotic shown to have anticancer activity and used in treatment of a
variety of cancers.
It inhibits transcription by binding to DNA at
the transcription initiation complex and
preventing elongation by RNA polymerase.
As it can bind DNA duplexes, it can also
interfere with DNA replication
2-Doxorubicin (adriamycin)
Mechanism of action
• Doxorubicin is anthracyclin antibiotic interferes with the
cells' production of DNA and RNA by inserting itself
between adjacent base pair causing local uncoiling thus
blocking DNA and RNA synthesis.
• Also its antitumor effect is related to its inhibition of
topoisomerase II enzyme (responsible for DNA repair).
• CYP 450 catalyzes the conversion of Doxorubicin into
semiquinone free radicals which produce superoxide
ion & H2O2 that mediate single strand scission in DNA
Uses
• Multiple cancers including breast, bone, ovarian &
leukemia.
• Acute lymphocytic leukemia (ALL).
• Non−Hodgkin's lymphoma
• Side effects
• A major problem with the use of doxorubicin is that it
cause irreversible heart problems specially heart failure
…….(why?)
• Hypersensitivity, myelosuppression
• Nausea, vomiting & diarrhea
• Urine and tears may take on a red color.
3-Mitomycin
• Mitomycin−C is an antitumor antibiotic. Mechanisimically
however, it belongs to DNA alkylating agents.
• Upon bioactivation inside the cell ,it preferentially
alkylates O6 of guanine base in DNA leading to cross
linking of DNA.
• It also degrade DNA through formation of free radicals.
• Side effects
– mitomycin−C may cause bone marrow suppression.
– Lung fibrosis may occur. If these lung problems do
occur, corticosteroids may provide effective therapy.
Stopping mitomycin−C therapy may also be
recommended.
4-Bleomycin
• It is cytotoxic in any phase of the cycle even on G0 phase
• Bleomycin degrade preformed DNA causing chain fragmentation and
release of free bases through the formation of free radicals
(superoxide and hydroxyl radicals).
Uses
• Bleomycin is used in the treatment of a number of different cancers,
including cancer of the head and neck, skin, esophagus, lung, testis,
and genitourinary tract.
• In addition, it is used in the treatment of Hodgkin's disease and
non−Hodgkin's lymphomas.
Side effects
• Pulmonary fibrosis
• Raynaud's phenomenon (which affects the fingers and toes, may
involve pain, pale color, and abnormal sensation as burning)
• In addition, headache, and nausea and vomiting may occur.
5-Procarbazine
• Procarbazine is an anticancer agent inhibits DNA and RNA
synthesis in cells
• interfering with mitosis.
Uses
• Procarbazine is used in the treatment of various cancers,
although the best established usage is with Hodgkin's disease.
• Other cancers in which procarbazine is sometimes used
include lymphomas, brain tumors, skin cancer, lung cancer,
and multiple myeloma.
Side effects
• it decreases the white blood cells and the platelet cells.
• The most severe side effect is nausea and vomiting.
• There may be neurological side effects such as confusion,
sleepiness, depression, nightmares, agitation, and
nervousness (it is weak MAOI………hypertension???)
Lecture No:03
IV-Plant
alkaloids
(Phase
specific
)
1-The vinca alkaloids
Vincristine & vinblastine (M-phase)
Mechanism of action
Tubulinmrof ot sesiremylop hcihw nietorp larutcurts a si microtubules.
The cell cytoskeleton and mitotic spindle, amongst other things, are
made of microtubules. Vincristine gntiibihni nilubut ot sdnib
eht fo notipursiD .serutcurts elubutorcim fo notiaziremylop
sdiolakla acniv ehT .esahpatem ni sisotim stserra selubutorcim
,sllec recnac gnidulcni sepyt llec gnidivid yldipar lla tceffa erofereht
.worram enob dna muilehtipe lantisetni osla tub
Side effects
The main side-effects of vincristine are peripheral neuropathy.
Accidental injection of vinca alkaloids into the spinal canal
(intrathecal administration) is highly dangerous, with a mortality rate
approaching 100 .%. vinblastin is less neurotoxic
Uses
• Non Hodgkin's& Hodgkin's disease, malignant lymphomas and
leukemia.
2-Taxanes
Paclitaxel & docetaxel
it is used for treatment of lung, ovarian and breast cancer.
Mechanism of action
paclitaxel hyper-stabilizes microtubule structure (freez them).
Paclitaxel binds to the β subunit of tubulin ,the resulting
microtubule/paclitaxel complex does not have the ability to
disassemble. This adversely affects cell function because the
shortening and lengthening of microtubules is necessary for their
function.
Further research has indicated that paclitaxel induces programmed
cell death (apoptosis) in cancer cells by binding to an apoptosis
stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting
its function.
Side effects
Bone marrow suppression and neurotoxicity
3-Etoposide
• Chemically it is deriven from podophyllotoxin, a toxin
found in the mandrake root.
• An inhibitor of the enzyme topoisomerase II .cause breaks
in the DNA inside the cancer cells and prevent them from
further dividing and multiplying. Then the cells die.
Side effect
• Vomiting & alopecia
• Bone marrow suppression
uses
• It has been useful for treatment of testicular cancer and
small cell lung cancer.
V-Miscellaneous cytotoxic drugs
1-Crisantaspase
• It is a preparation of asparaginase which kills cancer
cells by breaking down certain protein
(L−asparagine) that is necessary for survival and
growth . certain tumors are incapable of forming
such protein e.g. acute lymphoblastic leukemia ALL.
• Fortunately, normal cells are not dependent on
L−asparagine for survival.
• Asparaginase is mainly given in combination with
vincristine and steroids (either prednisone or
dexamethasone).
2-Mitotan
• effective in the treatment of adrenocortical
carcinoma.
• As a chemical, mitotane resembles the
insecticides DDD and DDT, although mitotane
does not harm people as these do. Scientists do
not understand why, but the drug causes damage
to the adrenocortex in such a way as to be helpful
for some patients with adrenocortical tumors. In
addition, mitotane restricts the ability of the
gland to produce steroids.
2- Hormones and
hormone antagonists
1-Corticosteroids
Corticosteroids have broad use in cancer
treatment. Some are used to treat adult leukemias,
adult lymphomas, and acute childhood leukemia.
Immunosuppressive mechanism
Glucocorticoids suppress the cell-mediated
immunity. They act by inhibiting genes that code for
the cytokines interlukin and TNF-γ, the most
important of which is the IL-2 .The inhibition of
cytokine production reduces the T cell proliferation.
Glucocorticoids also suppress the expansion and
antibody synthesis.
Side effects
Hyperglycemia due to increased gluconeogenesis, insulin
resistance caution in those with diabetes mellitus
reduced bone density (osteoporosis, higher fracture risk,
slower fracture repair)
weight gain due to increased visceral and truncal fat
deposition (central obesity) and appetite stimulation
adrenal insufficiency (if used for long time and stopped
suddenly without a tapering )
muscle breakdown (proteolysis), weakness; reduced muscle
mass and repair
growth failure, pubertal delay
Increased urea formation; negative nitrogen balance
The most common corticosteroids used in cancer treatment
are:
· dexamethasone (Decadron)
· hydrocortisone
· methylprednisolone (Medrol)
2-Estrogens & Progestons
Mainly used in androgen dependent prostatic tumors
3-Gonadotropin−releasing hormone analogues
Goserelin Acetate·
Goserelin acetate is a synthetic hormone that acts
similarly to the naturally occurring
gonadotropin−releasing hormone (GnRH). In men, this
results in decreased blood levels of the male hormone
testosterone. In women, it decreases blood levels of the
female hormone estrogen.
• It is used for treatment of breast and prostatic cancer
Side effects
• sweating ,hot flashes, impotence (erectile
dysfunction),sterility & gyncomestia
• depression or other mood changes
• Other common side effects in women include: light,
irregular, vaginal bleeding & no menstrual period
Hormone antagonists
Tamoxifen
• Tamoxifen selectively inhibits the effects of estrogen on breast
tissue, while selectively mimicking the effects of estrogen on bone
(by increasing bone mineral density) and uterine tissues. These
qualities make tamoxifen an excellent therapeutic agent against
breast cancer. it is known to compete with estrogen by binding to
estrogen receptors on the membrane of target cells, thus limiting
the effects of estrogen on breast tissue.
• Tamoxifen may also has other anti−tumor activities :affecting
oncogene expression& promotion of apoptosis (cancer cell death)
Adverse Effects
• CNS: Depression, light headedness, dizziness, headache, decreased
visual acuity &retinopathy
• GI: Nausea, vomiting
• Hematological: Hypercalcemia
• GU: Vaginal bleeding, vaginal discharge & menstrual irregularities
• Dermatologic: Hot flashes, skin rash
Lecture No:04
3-Immunomodulators
Immune system and cancer
• The immune system serves as one of the primary
defenses against cancer. When normal tissue
becomes a tumor or cancerous tissue, new antigens
develop on their surface. These antigens send a
signal to immune cells such as the T lymphocytes
and macrophages, which in turn directly kill the
tumor cells or release substances like cytokines that
may bring about tumor cell death.
Immunomodulators
Immunosuppressant
Immunostimulants
a-Immunosuppressant
1 Glucocorticoids
2 Cytotoxic
a- Alkylating agents
b- Antimetabolites
1 Methotrexate
2.Azathioprine and Mercaptopurine
3. Drugs acting on immunophilins
1 Cyclosporin
2. Sirolimus
Drugs acting on immunophilins
Cyclosporin
is a calcineurin inhibitor. is one of the most widely used
immunosuppressive drugs. It is a fungal peptide, composed
of 11 amino acids.
• Cyclosporin is thought to bind to the cytosolic protein
cyclophilin (an immunophilin) of immunocompetent
lymphocytes, especially T-lymphocytes. This complex of
cyclosporin and cyclophilin inhibits calcineurin, which
under normal circumstances induces the transcription of
interleukin-2. The drug also inhibits lymphokine production
and interleukin release, leading to a reduced function of
effector T-cells.
• Cyclosporin is used in the treatment of acute rejection
reactions, but has been increasingly substituted with newer
immunosuppressants, as it is nephrotoxic.
Sirolimus
• Sirolimus is a macrolide lactone, produced by the
Streptomyce hygroscopicus It is used to prevent
rejection reactions. Although it is a structural analogue
of tacrolimus, it acts somewhat differently and has
different side effects.
• Contrary to cyclosporine that affect the first phase of
the T lymphocyte activation, sirolimus affects the
second one, namely the signal transduction and their
clonal proliferation. Therefore, sirolimus acts
synergistically with cyclosporine and, in combination
with other immunosuppressants, has few side effects.
Indirectly it inhibits several T lympohocyte kinases and
phosphatases, preventing the transmission of signal
into their activity and the transition of the cell cycle
from G1 to S phase. Similarly, it prevents the B cell
differentiation to the plasma cells, which lowers the
quantity of IgM, IgG and IgA antibodies produced. It
acts immunoregulatory.
b-Immunostimulants
Biologic therapy, also called
immunostimulants, is a treatment that uses
drugs to improve the way your body’s immune
system fights disease. Your immune system is
your body’s natural defense against disease. A
healthy and strong immune system can detect
the difference between healthy cells and
cancer cells. Biologic therapy attempts to
stimulate, or enhance the immune system so
that it can fight the cancer
1-Monoclonal Antibodies
Monoclonal antibodies are proteins produced in the laboratory from
a single clone of a B−cell, the type of cells of the immune system that
make antibodies. When used as a treatment for cancer, there are
three general strategies with monoclonal antibodies:
• One uses the ability of the antibodies to bind to the cancer cells
having the tumor antigens on their surface. The immune system will
see the cancer cells marked with bound antibodies as foreign and
destroy them.
• A second strategy is to use the antibodies to block the binding of
cytokines or other proteins that are needed by the cancerous cells to
maintain their uncontrolled growth. Monoclonal antibodies designed
to work like this bind to the cytokine receptors that are on the tumor
cell surface.
• A final strategy involves special antibodies that are linked
(conjugated) to a substance that is deadly to the cancer cells. E.G.
radioactive isotopes, have been successfully conjugated to
antibodies. The antibodies are then used to specifically destroy he
tumor cells with the radioactivity or toxic substance.
Trastuzumab
• Trastuzumab is a humanized monoclonal
antibody produced by recombinant DNA
technology that binds specifically to the
human epidermal growth factor receptor 2
protein (also known as HER2) that is found on
the cell surface of some cancer tumors, most
notably breast cancer(25−30% of breast
malignancies) and also targets it for
destruction by the natural killer cells of
immune system.
2-Biological response modifiers
Researchers have been working on
stimulating the immune cells during cancer
with substances broadly classified as
biological response modifiers. Cytokines
are one such substance. These are proteins
that are predominantly released by
immune cells upon activation or
stimulation.
Aldesleukin
Aldesleukin is interleukin, that is used to treat metastasis renal cell
carcinoma (a form of kidney cancer) and metastasis melanoma.
Aldesleukin is also known as interleukin−2, IL−2
When renal cell carcinoma and metastasis melanoma (cancer of the
skin that arises in the pigmented cells of the skin or eyes) do not
respond to other therapies, they are candidates for treatment with
aldesleukin.
Aldesleukin is a biological response modifier (BRM). It promotes the
development of T cells, or the cells in the lymphatic system that can
fight cancer cells.
Side effect
Flu-like symptoms (chills, fever, fatigue)
Loss of appetite
Skin problems such as a rash, itchiness, scaling
Cardiac arrhythmias
Gastrointestinal disturbance, such as nausea and vomiting
Neurological effects, such as depression and poor concentration
Interferons
Interferons are small, natural cytokines that are produced by leucocytes
,T−lymphocytes, and fibroblasts in response to infection and other
biological stimuli.
The goal of interferon use is to activate tumor−specific cytotoxic
T−lymphocytes. Thus, tumor cells would be destroyed based on
immunotherapy.
Interferons attach to special receptors on the surface of cell
membranes. Then produce variety of functions including enhancing or
inhibiting enzymes, decreasing cell proliferation, or enhancing the
activity of macrophages and T−lymphocytes. There are several different
classes of interferons, cancer therapy primarily focuses on alpha
interferons.
Alpha interferons are used to treat cancers such as hairy cell leukemia,
malignant melanoma, and Kaposi's sarcoma (an AIDS−related cancer) as
well as many other cancers
Side effects
muscle aches, unusual metallic taste in the mouth, fever and chills, and
general flu−like symptoms such as headache, loss of appetite (anorexia),
nausea and vomiting, and fatigue. To reduce the flu−like symptoms
physicians may suggest that the patient take acetaminophen before
each dosage.
confusion, trouble thinking and focusing, mental depression,
nervousness, or numbness or tingling of fingers,
Levamisole
Levamisole act to restore depressed immune function. It
increases the response of T cells, or cells belonging to the
lymphatic system that can fight cancer cells. It also seems to
increase the activity of cells that attack and destroy invading
cancer cells, including both monocytes and macrophages.
Side Effects
Allergic reaction.
Decreased bone marrow function, resulting in fatigue or
signs of infection
Problems related to the nervous system, such as confusion,
loss of consciousness, or speech disturbances
3-Angiogenesis inhibitors
• Angiogenesis is the normal process by which the
human body forms new blood vessels. Angiogenesis
is important in the development of cancer because
tumors require blood vessels to grow and spread to
nearby tissue. Once a tumor reaches a certain size it
needs to develop a blood supply in order to grow.
Cancer cells will secrete certain chemicals to
promote angiogenesis. Angiogenesis inhibitors are
drugs that can stop this process. These antiangiogenesis agents are being investigated as
potential cancer therapies.
Thalidomide
Thalidomide interferes with the growth of rapidly dividing
cells.It interferes with the formation of blood vessels. It is
called an antiangiogenic drug
It is used to treat several types of cancers, including kidney,
ovarian, and breast cancer.
Side effects :
Orthostatic hypotension
Thalidomide may cause peripheral neuropathy (numbness,
tingling, pain, or burning sensations in the feet or hands).
Thalidomide may cause severe birth defects or fetal death if
taken by pregnant women (phocomelia).
Rash
Lack of bowel movements
Good luck