Types
The majority of chemotherapeutic drugs can be divided in to
alkylating agents,
antimetabolites,
anthracyclines, plant
lkaloids,
topoisomerase inhibitors, and other antitumour agents. All of these drugs
affect
ell
division or NA
synthesis and function in some way.
Some newer agents don't directly interfere with DNA. These include
monoclonal antibodies and the new
tyrosine kinase inhibitors e.g.
matinib
mesylate (Gleevec or Glivec), which directly targets a
molecular abnormality in certain types of cancer (hronic
myelogenous leukemia,
gastrointestinal stromal tumors).
In addition, some drugs may be used which modulate tumor cell behaviour
without directly attacking those cells. Hormone treatments fall into this
category of adjuvant therapies.
Where available,
Anatomical Therapeutic Chemical Classification System codes are provided for
the major categories.
Alkylating agents (L01A)
-
Main article:
Alkylating antineoplastic agent
Alkylating agents are so named because of their ability to add alkyl groups
to many
electronegative groups under conditions present in cells.
isplatin
and
carboplatin, as well as
oxaliplatin are alkylating agents.
Other agents are
mechlorethamine,
cyclophosphamide,
chlorambucil. They work by chemically modifying a cell's DNA.
Anti-metabolites (L01B)
-
Main article:
antimetabolite
Anti-metabolites masquerade as
urine
((azathioprine,
mercaptopurine)) or
yrimidine
- which become the building blocks of DNA. They prevent these substances
becoming incorporated in to DNA during the "S" phase (of the
ell cycle),
stopping normal development and division. They also affect RNA synthesis. Due to
their efficiency, these drugs are the most widely used cytostatics.
Plant alkaloids and terpenoids (L01C) These
alkaloids are derived from
lants and block
cell division by preventing
microtubule function. Microtubules are vital for cell division and without
them it can not occur. The main examples are
vinca alkaloids and
axanes.
Vinca alkaloids (L01CA)
Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of
tubulin into microtubules (
phase of the
ell cycle).
They are derived from the
Madagascar periwinkle, Catharanthus roseus (formerly known as
Vinca rosea). The vinca alkaloids include:
-
Vincristine
-
Vinblastine
-
Vinorelbine
-
Vindesine
Podophyllotoxin (L01CB)
Podophyllotoxin is a plant-derived compound used to produce two other
cytostatic drugs,
toposide
and
teniposide. They prevent the cell from entering the
1 phase
(the start of DNA replication) and the replication of DNA (the
phase). The
exact mechanism of its action still has to be elucidated.
The substance has been primarily obtained from the
American Mayapple (Podophyllum peltatum). Recently it has been
discovered that a rare
Himalayan Mayapple (Podophyllum hexandrum) contains it in a much
greater quantity, but as the plant is endangered, its supply is limited. Studies
have been conducted to isolate the genes involved in the substance's production,
so that it could be obtained
recombinantively.
Taxanes (L01CD)
The prototype taxane is the
natural product
aclitaxel,
originally known as
Taxol and first derived from the bark of the
Pacific Yew tree.
ocetaxel
is a semi-synthetic analogue of paclitaxel. Taxanes enhance stability of
microtubules, preventing the separation of
hromosomes
during naphase.
Topoisomerase inhibitors (L01CB and L01XX)
Topoisomerases are essential
nzymes that
maintain the
topology of DNA. Inhibition of type I or type II topoisomerases interferes
with both
transcription and
replication of DNA by upsetting proper DNA
supercoiling.
- Some type I topoisomerase inhibitors include camptothecins:
irinotecan and
opotecan.
- Examples of type II inhibitors include
msacrine,
toposide,
etoposide phosphate, and
teniposide. These are semisynthetic derivatives of
epipodophyllotoxins, alkaloids naturally occurring in the root of
American Mayapple (Podophyllum peltatum).
Antitumour antibiotics (L01D) See main article:
antineoplastic
The most important immunosuppressant from this group is
dactinomycin, which is used in
kidney transplantations.
Monoclonal antibodies
Monoclonal antibodies work by targeting tumour specific antigens, thus
enhancing the host's immune response to tumour cells to which the agent attaches
itself. Examples are
trastuzumab (Herceptin),
etuximab,
and ituximab
(Rituxan or Mabthera).
Bevacizumab (Avastin) is a monoclonal antibody that does not directly attack
tumor cells but instead blocks the formation of new tumor vessels.
Hormonal therapy Several malignancies respond to
hormonal therapy. Strictly speaking, this is not chemotherapy. Cancer
arising from certain tissues, including the mammary and prostate glands, may be
inhibited or stimulated by appropriate changes in hormone balance.
- teroids
(often
dexamethasone) can inhibit tumour growth or the associated
dema (tissue
swelling), and may cause regression of lymph node malignancies.
Dexamethasone is also an
antiemetic, so it may be used with cytotoxic chemotherapy even if it has
no direct effect on the cancer.
-
Prostate cancer is often sensitive to
finasteride, an agent that blocks the peripheral conversion of
testosterone to
dihydrotestosterone.
-
Breast cancer cells often highly express the
strogen
and/or
progesterone receptor. Inhibiting the production (with
aromatase inhibitors) or action (with
amoxifen)
of these hormones can often be used as an adjunct to therapy.
- Gonadotropin-releasing hormone agonists (GnRH), such as
oserelin
possess a paradoxical negative feedback effect followed by inhibition of the
release of FSH (ollicle-stimulating
hormone) and LH (uteinizing
hormone), when given continuously.
Some other tumours are also
ormone
dependent, although the specific mechanism is still unclear.
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