Dr.
Jawad Sodhar
Cancer is a disease characterized by a
loss in the normal control mechanisms
that govern cell survival, proliferation,
and differentiation.
Chemicals
Pollutants
Viruses
Surgical removal
Radiotherapy
Chemotherapy
Endocrine therapy
Immunotherapy
Cryotherapy
Laser therapy
Primary surgery plus chemotherapy is very effective for localized tumors
Cytotoxic chemotherapy is curative for only certain types of cancers
e.g. testicular tumors, Wilim’s tumor
Chemotherapy usually prolongs life but patient ultimately dies of due
to disease.
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Symptoms%20and%20Therapy_files/image001.jpg
1 . G1 phase:
cell prepares for DNA synthesis
2 . S phase
a DNA synthesis phase (cell generates complete copy of genetic material)
3 . G2 phase:
cell prepares for mitosis
4 . M phase:
the mitotic phase (in which the cell, containing a double complement of
DNA, divides into two daughter G1 cells)
G0 phase:
resting state (each of these daughter cells may immediately re-enter the
cell cycle or pass into a nonproliferative stage, referred to as G0).
1. Antimetabolites Folic acid Antagonists
Methotrexate
Purine antagonists: 6- mercaptopurine, 6- thioguanine
Pyramidine antagonists: 5- Flourouracil, Cydarabine
2. Plant alkaloids:
Vincristine, Vinblastine, Etoposide
contd.
3. Alkylating Agents:
Cyclophosphamide, Melphalan, Chlorambucil,
Busulphan, Lomustine, Carmustine, Cisplatin.
Mechlorethamine, Procarbazine, Decarbazine,
4. Antibiotics:
Dactinomycin, Doxorubicin, Daunorubicin,
Bleomycin, Plicamycin, Mitomycin.
5. Hormones & Hormonal antagonists:
Prednisolone, estrogen, Tamoxifen, Flutamide
6 Topoisomerase 1 inhibitors:
Etoposide
7. Topoisomerase 11 inhibitors:
Irinotecan, Topotecan
8. Miscellaneous:
L- Asparaginase
MATINIB, DASATINIB, & NILOTINIB (inhibitor of the tyrosine
kinase domain)
Act against all cells which are multiplying i.e.
oBone marrow
oMucosal surfaces (gut)
oHair follicles
oGerm cells
oReticuloendothelial system
1. Antimetabolites Folic acid Antagonists
Methotrexate
Purine antagonists:
6- mercaptopurine,
6- thioguanine
Pyramidine antagonists:
5- Flourouracil, Cydarabine
Mechanism of action
mechanism of action
Antimetabolite (antifolates)
disruption of folate-dependent metabolic processes
essential for cell replication by inhibition of
dihydrofolate reductase
glycinamide ribonucleotide formyltransferase
thymidylate synthase
purine analogues interference
pirimidine analogues with synthesis
adenosine analogues of DNA precursors
2. Alkylating Agents
Cyclophosphamide
Melphalan
Chlorambucil
Busulphan
Lomustine
Carmustine
Cisplatin
Mechlorethamine
Procarbazine
Decarbazine
mechanism of action
alkylating agents
the alkylating agents exert their cytotoxic effects via
transfer of their alkyl groups to various cellular
constituents However;
these drugs react chemically with sulfhydryl, amino,
hydroxyl, carboxyl, and phosphate groups of other
cellular nucleophiles , resulting the cell death.
3. Anti-Tumor Antibiotics
Dactinomycin
Doxorubicin
Daunorubicin
Bleomycin
Plicamycin
Mitomycin
mechanism of action
Antitumor antibiotics
Many of these antibiotics bind to DNA and block
the synthesis of RNA, DNA, or both and interfere
with cell replication.
Topoisomerase 1 inhibitors:
Etoposide
Topoisomerase 11 inhibitors:
Irinotecan, Topotecan
mechanism of action
topoisomerase inhibitors
► Topo I inhibitors
interruption of the elongation phase of DNA
replication
► Topo II inhibitors
stabilization of the DNA-topo complex, leading
to inability to synthesize DNA.
Plant alkaloids
Vincristine
Vinblastine
mechanism of action
Vinca alkaloids
tubulin binding
blockage of microtubule polimerization
impaired mitotic spindle formation
Taxanes
mechanism of action
promotion of microtubule assembly and stability
M phase block
induction of apoptosis
Anal carcinoma
Bladder carcinoma
Breast cancer
Laryngeal cancer
Osteogenic sarcoma
Soft tissue sarcomas
Indications cont:
•Non–small cell lung cancer
•Breast cancer
•Esophageal cancer
•Nasopharyngeal cancer
•Other cancers of the head and neck region
•Pancreatic cancer
•Gastric cancer
•Prostate cancer (hormones)
•Cervical carcinoma
Hormonotherapy
mechanism of action
► hormone deprivation
removal of hormone producing tissue (ablation)
inhibition of hormone production
blocking of hormone receptors
► exogenous hormone treatment (additive therapy)
Hormonotherapy – indications
breast cancer
prostate cancer
endometrial cancer
renal cancer
ovarin cancer
cancer cachexia
COMMON TOXICITIES OF CHEMOTHERAPY
► gonadal damage
sterility
hormonal changes
► organ damage
cardiotoxicity
pulmonary damage
hepatotoxicity
nephrotoxicity
► neuroxicity
► local
complications (extravasation)
► secondary malignancies
COMMON TOXICITIES OF CHEMOTHERAPY
► myelosuppression
► immunosuppression
► alopecia
► diarrhea
► flu-like symptoms
Methotrexate :
Crystalluria. Nephrotoxicity
Alkylating agents:
Mutagenic & carcinogenic
Daunorubicin & doxorubicin :
Cardiotoxic
Plicamycin:
Hepatotoxic
Bleomycin :
Anaphylactic shock.
Give intermittent therapy.
Emesis is controlled by ondanseteron, aternatively
metoclopramide or domperidone can be given.
Bone marrow suppression is corrected by giving
Erythropoietin and colony stimulating factors.
Interferons can be given to boost immunity
Summary of mechanisms and sites of action
Thanks
