Unformatted text preview: Cancer and Anti
Cancer and Anti
Cancer Drugs Cancer
Cancer ► The oldest description of human cancer was found in an Egyptian papyrus about 2000 BC. The oldest specimen of a human cancer was found in a female skull ca 1600 BC. The skeletal remains of Peruvian Incas, ca 400 BC, contained lesions suggestive of malignant melanoma. ► Hippocrates was the first to recognize the difference between benign and malignant tumors . The swollen blood vessels around the malignant tumors so reminded him of crab claws, he called the disease karkinos (crab). ► Cancer is a class of diseases characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either directly or by implantation into distant sites by metastasis. Classification
► Carcinoma: tumors derived from epithelial cells, including forms of breast, prostate, lung and colon cancer. Lymphoma and Leukemia: tumors derived from blood and bone marrow cells Sarcoma: tumors derived from connective tissue, or mesenchymal cells (from the embryonic mesoderm) Glioma: tumors derived from brain cells Germ cell tumors: tumors derived from germ cells, found in the testicle and ovary Choriocarcinoma: tumors derived from the placenta Cancer Statistics
► In 2008 7.6 million people died of cancer worldwide.
► The most common being: lung cancer
breast cancer cancer is the leading cause of death.
2.6 million are diagnosed with cancer every year
over half the men in China from smoke tobacco
Lung cancer is the commonest form of cancer in China. Deaths from this disease have shot up fivefold since the 1970s ► In China Smoking and Lung Cancer
Smoking and Lung Cancer ► Genetic Causes of Cancer
Causes of Cancer ► Viral ►Herpes virus Kaposi sarcoma ►Human papilloma viruses Cervical cancer
►Retroviruses Feline leukemia ► Environmental ►Food: dietary factors; free radical genesis
►Air: cigarette smoke; asbestos
►Water: pesticides ►Radiation: Xrays, UV, Cosmic rays. Cancer Prevention
► Cancer is considered a largely preventable disease. Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: Tobacco usage
Alcohol over consumption
Sexually transmitted infections (AIDS)
Other cases of cancer are caused through hereditary genetic disorders, and thus it is not possible to prevent all cases of cancer. Diet and Cancer
Diet and Cancer
► The primary dietary factors that increase risk are obesity and alcohol consumption
a diet low in fruits and vegetables
high in red meat/and overzealous meat consumption Consumption of coffee is associated with a reduced risk of liver cancer. Studies have linked consumption of red or processed meat to an increased risk of breast cancer, colon cancer, and pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in foods cooked at high temperatures. Characteristics of Cancer Cells
• Cancer cells
– Have abnormal nucleus
– Lose normal control and divide indefinitely
– They do not undergo apoptosis
– They metastasize: spread to other areas
– They promote the formation of new blood
– Telomeres do not shorten upon cell-division DNA REPLICATION
DNA REPLICATION Antineoplastic Mechanisms
Transcription TRANSLATION Significance of the CellCycle in Cancer Significance of the Cell Cycle in Cancer Therapy
► Cell cycle Specific Agents Drugs effective at specific stages of growth: e.g . Bleomycin inhibits G2
► Cell Cycle Non Specific Agents: Drugs that interfere at any interval in the cell cycle.
►Alkylating agents interfere with replication during all phase of the cell cycle. It is independent of the cycling. Cell Cycle Inhibition
VePesid 6mercaptopurine Cell Cycle Inhibitors
Cell Cell Cycle Inhibition
Cell Cycle Inhibition
Methotrexate/5FU Nitrogen mustard/ Nitrosourea Doxorubicin/Dactinomycin Vinblastine/Vincristine AntiNeoplastic Drug Classification…..
AntiNeoplastic Drug Classification…..
► Alkylating Agents Nitrogen mustard ► Cyclophosphamide Nitrosoureas ► Antimetabolites Folic Acid analog
► Methotrexate Pyrimidine analog ► Fluorouracil (5FU) Purine analog ► Mercaptopurine (6MP) AntiNeoplastic Drug Classification
AntiNeoplastic Drug Classification
► Plant Alkaloids Vincristine Vinblastine VePecid-16
► Antibiotics Dactinomycin
► Hormone analogs Tamoxifen (Antiestrogenic) Alkylating Agents
Alkylating Agents Nitrogen mustards Defined by having two
choloro substituents on
the same nitrogen.
the They all have the
CH ► Targets Purine and pyridine bases in
DNA binding to C, O or N in
the target molecule.
They form a crosslink within
the same DNA or between two
strands of DNA inhibiting
separation of the DNA strands
resulting in cell death.
resulting Alkylating Agents
► Nitrogen Mustard Used to treat Hodgkin’s lymphoma*, lung, breast and ovarian
cancer. ► Cyclophosphamide
Toxic metabolites are known to affect the bladder and kidney.
Used to treat leukemias, lymphomas and breast cancers. Hodgkin's disease, characterized by a particular cell
known as the Reed-Sternberg cell.
► ► ► ► This group also works by
cross-linking proteins or
They are very lipophilic which
enables them to cross the
BBB and act against tumors
of the CNS
Because of their long-lasting
effect on the WBC population
they are administered every 68 weeks.
Applied against lung, brain
and gastrointestinal tumors. Adverse Effects
Adverse Effects Antimetabolites
Antimetabolites Synthetic analogs of nucleic acid bases resulting in an abnormal DNA
► ► ►
► ► Methotrexate is a folic
acid analog which
reductase resulting in the
stoppage of DNA
The drug is well absorbed
either orally or
It crosses the BBB.
High doses (0.2-20g) are
sometimes required in
The drug is used to treat
sarcomas and breast
cancer. Folate Metabolism
Folate Metabolism DNA PURINES
► Adenine PYRIMIDINES
► Thymine ► Cytosine
► Uracil Mitotic inhibitors
► Vincristine and vinblastine derived from the periwinkle plant.
► They bind to tubulin and inhibit spindle formation preventing the cells from undergoing mitosis (see fig).
► Both drugs are given intravenously and eliminated by hepatic biotransformation.
► Used in the treatment of breast cancer, testicular cancer, and sarcoma.
► Adverse reactions include bone marrow suppression and neuropathy. Mitosis Mitosis Periwinkle
Periwinkle TAMOXIFEN:Hormone Analog
This is an anti-estrogen
► It binds to the estrogen
receptor and inhibits
DNA and RNA synthesis.
► It decreases levels of
circulating prolactin, LH
► It is used extensively for
treatment of breast cancer.
Antiestrogen Antineoplastic Agents: side effects Antineoplastic Agents: side effects Leukopenia, neutropenia,
► Blood clots (thrombosis), stroke
► Endometrial cancer, endometriosis
► Fertility issues
► Hair thinning
► Oral inflammation glossitis, xerostomia, stomatitis, teeth and
gum sensitivity SUMMARY
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- Winter '10
- DNA, Chemotherapy