2. Cancers are classified by the type of cellthat the
tumor cells resemble and is therefore presumed to
be the origin of the tumor. These types include:
Carcinoma: Cancers derived from epithelial cells.
This group includes many of the most common
cancers and include nearly all those in
the breast, prostate, lung, pancreas and colon
Sarcoma: Cancers arising from connective
tissue (i.e. bone, cartilage, fat, nerve), each of
which develops from cells originating
in mesenchymalcells outside the bone marrow.
3. Lymphoma and leukaemia: These two classes
arise from hematopoietic (blood-forming) cells
that leave the marrow and tend to mature in
the lymph nodes and blood, respectively.
Germ cell tumor Cancers derived
from pluripotent cells, most often presenting in
the testicle or
the ovary (seminoma and dysgerminoma,
respectively).
Blastoma: Cancers derived from immature
"precursor" cells or embryonic tissue.
7. It has been derivatized into the estrogen analogue estramustine phosphate,
used to treat prostate cancer. It can also be used in chemical warfare where it
has the code-name HN2. This chemical is a form of nitrogen mustard gas and
a powerful vesicant. Historically, some uses of mechlorethamine have
included lymphoid malignancies such as Hodgkin’s disease, lymph sarcoma,
chronic myelocytic leukaemia, polycythaemia vera, and bronchogenic
carcinoma
8.
also known as cytophosphane among other names, is a medication used
as chemotherapy and to suppress the immune system. As chemotherapy it is
used to treat lymphoma multiple myeloma leukaemia, ovarian cancer, breast
cancer, small cell lung cancer, neuroblastoma and sarcoma.
MOA: The main effect of cyclophosphamide is due to its metabolite phosphor
amide mustard. This metabolite is only formed in cells that have low levels
of ALDHAldehyde dehydrogenase. Phosphor amide mustard forms DNA
crosslinks both between and within DNA strands at guanineN-7 positions
(known as interstrand and intrastrand crosslinkages, respectively). This is
irreversible and leads to cell apoptosis
9. Malphalan chemically alters
the DNA nucleotide guanine through alkylation, and causes
linkages between strands of DNA. This chemical alteration
inhibits DNA synthesis and RNA synthesis, functions necessary
for cells to survive. These changes cause cytotoxicity in both
dividing and non-dividing tumor cells.
10. Chlorambucil produces its anti-cancer effects by interfering with
DNA replication and damaging the DNA in a cell. The DNA damage
induces cell cycle arrest and cellular apoptosis via the accumulation of
cytosolic p53 and subsequent activation of Bcl-2-associated X protein,
an apoptosis promoter. Chlorambucil alkylates and cross-links DNA
during all phases of the cell cycle, inducing DNA damage via three
different methods of covalent adduct generation with double-helical
DNA
11. Busulfan is an alkylsulfonate It is an alkylating agent that forms DNA-
DNA intrastrand
crosslinks betweenthe DNAbases guanine and adenine and
between guanin and guanine.This occurs through an SN2 reaction in
which the relatively nucleophilicguanine N7 attacks the carbon adjacent
to the mesylate leaving group. DNA crosslinkingprevents DNA
replication Because the intrastrand DNA crosslinks cannot be repaired by
cellular machinery, the cell undergoes apoptosis
12. Thiotepa is an organophosphorus compound with the formula SP(NC2H4)3.[2] It is
an analogue N,N′,N′′-triethylenephosphoramide (TEPA), which contains
tetrahedral phosphorus and is structurally akin to phosphate. It is manufactured
by heating aziridine with thiophosphoryl chloride. Thiotepa is indicated for use in
combination with other chemotherapeutic agents. This can be with or without total
body irradiation (TBI), as a conditioning treatment prior to allogeneic or
autologous hematopoietic progenitor cell transplantation (HPCT)
in haematological diseases in adult and paediatric patients.
13. Antimetabolite drugs were among the first effective chemotherapeutic
agents discovered. Classified as folic acid, pyrimidine or purine
analogues, these compounds have similar chemical structures to
molecules the body uses in nucleic acid (DNA and RNA) synthesis.
(6-MP) is another purine agent used against acute lymphocytic
leukaemia. It is active in the S phase of cell proliferation. When it is
incorporated into DNA and RNA, the nucleic acids are rendered useless.
6-MP may also act through inhibition of de novo synthesis of the purine
bases. Genetic mutation may lead to purine resistance.
14. 6-Thioguanine is a thio analogue of the naturally occurring purine base
guanine. 6-thioguanine utilises the enzyme hypoxanthine-guanine
phosphoribosyltransferase (HGPRTase) to be converted to 6-thioguanosine
monophosphate (TGMP). High concentrations of TGMP may accumulate
intracellularly and hamper the synthesis of guanine nucleotides via the
enzyme Ionise monophosphate dehydrogenase (IMP dehydrogenase)
15. 5-FU acts in several ways, but principally as a thymidylate synthase (TS)
inhibitor. Interrupting the action of this enzyme blocks synthesis of the
pyrimidine thymidine, which is a nucleoside required for DNA
replication. Thymidylate synthase methylates deoxyuridine
monophosphate (dUMP) to form thymidine monophosphate (dTMP).
Administration of 5-FU causes a scarcity in dTMP, so rapidly dividing
cancerous cells undergo cell death .
16. Floxuridine is rapidly catabolized to 5-fluorouracil which is the active
form of the drug. The primary effect is interference with DNA synthesis
and to a lesser extent, inhibition of RNAformation through the drug's
incorporation into RNA, thus leading to the production of fraudulent
RNA. Fluorouracil also inhibits uracil ribose phosphorylate which
prevents the utilization of preformed uracil in RNA synthesis. As well,
the monophosphate of floxuridine, 5-fluoro-2'-deoxyuridine-5'-
phsphate(FUDR-MP) inhibits the enzyme thymidylate synthetase
17. Cytosine arabinoside combines a cytosine base with an arabinose sugar. It is an antimetabolic
agent with the chemical name of 1β-arabinofuranosylcytosine. Certain sponges, where it was
originally found, use arabinoses sugars to form a different compound (not part of DNA).
Cytosine arabinoside is similar enough to human deoxycytosine to be incorporated into human
DNA, but different enough that it kills the cell. Cytosine arabinoside interferes with the
synthesis of DNA. Its mode of action is due to its rapid conversion into cytosine arabinoside
triphosphate, which damages DNA when the cell cycle holds in the S phase (synthesis of
DNA). Rapidly dividing cells, which require DNA replication for mitosis, are therefore most
affected.
18. In cell biology, actinomycin D is shown to have the ability to
inhibit transcription. Actinomycin D does this by binding DNA at the
transcription initiation complex and preventing elongation of RNA chain
by RNA polymerase
19. Doxorubicin interacts with DNA by intercalation and inhibition of
macromolecular biosynthesis. This inhibits the progression
of topoisomerase II, an enzyme which relaxes supercoils in DNA
for transcription. Doxorubicin stabilizes the topoisomerase II complex
after it has broken the DNA chain for replication, preventing the DNA
double helix from being resealed and thereby stopping the process
of replication. It may also increase Quinone type free radical production,
hence contributing to its cytotoxicity
20. Bleomycin acts by induction of DNA strand breaks. Some studies
suggest bleomycin also inhibits incorporation of thymidine into
DNA strands. DNA cleavage by bleomycin depends on oxygen
and metal ions, at least in vitro. The exact mechanism of DNA
strand scission is unresolved, but it has been suggested that
bleomycin chelates metal ions (primarily iron), producing a
pseudoenzyme that reacts with oxygen to produce superoxide and
hydroxide free radicals that cleave DNA.