1. Cancer treatment and chemotherapy11
Cancer treatment and chemotherapy

2. Cancer
Cancer is a group of more than 100 different diseases, characterized by uncontrolled cellular growth, local tissue invasion, and distant metastases.

3. Etiology of cancer
A cancer, or neoplasm, is thought to develop from a cell in which the normal mechanisms for control of growth and proliferation are altered.

4. Carcinogenesis
Substances that may act as carcinogens include chemical, physical, and biological agent.
Exposure to chemicals may occur by virtue of occupational and environmental means, as well as lifestyle habits. For example
Exposure to aniline dye cause bladder cancer
Exposure to Benzene cause some leukemia.
Some drugs and hormones used for therapeutic purposes cause cancer in human include

5. Drug or Hormone
Type of cancer caused
Alkylating agents ( e.g. chlorambucil, mechlorethamine, carmustine)
leukemia
Anabolic steroids
Liver
Analgesic containing phenacetin
Renal , urinary bladder
Antiestrogen ( tamoxifen)
Endometrium
Coal tars ( topical)
Skin
Nonsteroidal Estrogens (diethylstilbestrol)
vagina/ cervix, endometrium , breast , testes
Steroidal ( estrogen replacement therapy, oral contraceptive )
Endometrium, breast, liver
Epipodophyllotoxins ( etoposide, teniposide)
Leukemia
Immunosuppressive drugs ( cyclosporine, azathioprine)
lymphoma, skin
Nitrogen mustard derivatives ( cyclophosphaide, ifosfamide)
Urinary bladder , leukemia

6. Physical agents that act as carcinogens include ionizing radiation and ultraviolet light.
Viruses are biologic agents that are associated with certain cancers. Example
Epstein- Barr virus is an important factor in the initiation of African Burkitts lymphoma.
Infection with hepatitis B virus is known to be a major cause of hepatocellular cancer.

7. Genetic basis of cancer
There are two major classes of genes involved in carcinogenesis:
Activation Oncogenes
Inactivation Tumor- suppressor genes
Another group of genes important in carcinogenesis is the DNA repair genes. The normal function of these genes is to repair DNA that is damaged by environmental factors, or errors in DNA that occur during replication. If not corrected, these errors can result in mutations that activate oncogenes or inactivate tumor suppressor genes.

8. Pathogenesis of cancer

9. Invasion and metastasis
Metastasis is the spread of neoplastic lesion cells from the primary tumor site to distant sites. The two primary pathways of metastasis are 1- hematogenous 2- lymphatic

10. Types of tumors Tumor may be either benign or malignant. Benign tumor
Malignant tumor
Rate of growth/
slow
Rapid
localized
Invades and destroy the surrounding tissue
These masses rarely metastasize, and once removed they rarely recur
metastasize
Cells of benign tumors resemble the cells from which they developed.
The cells of malignant tumors are genetically unstable, and loss of normal architecture results in cells that are atypical of their tissue or cells of origin.

11. Tumor origin Tumors may arise from any of four basic tissue types:
Epithelial tissue
Connective tissue
Lymphoid tissue and hematopoietic cells
Nerve tissue

12. Cancer classification by tissue type
Tissue of origin
Malignant
Epithelial/
Surface epithelium
Glandular tissue
Carcinoma ( squamous, epidermoid)
Adenocarcinoma
Connective tissue /
Fibrous tissue
Bone
Smooth muscle
Striated muscle
Fat
Fibrosarcoma
Osteosarcoma
Leiomyosarcoma
Rhabdomyosarcoma
liposarcoma
Lymphoid tissue and hematopoietic cells/
Bone marrow elements
Lymphoid tissue
Plasma cell
Leukemia
Hodgkin s and non Hodgkin s lymphoma
Multiple myeloma
Neural tissue/
Glial tissue
Nerve sheath
melanocytes
Glioblastoma multiforme, astrocytoma
Neurofibrosarcoma
Malignant melanoma

13. Staging of cancers
The most commonly applied staging system for solid tumors is the TNM classification, where T= tumor, N= node, and M= metastases.
The designated rating for tumor describes the size of the primary mass and ranges from T1 to T4.
Nodes are described in terms of the extent and quality of nodal involvement ( N0 to N3).
Metastases are generally scored depending on their presence or absence (M0 or M1).

14. The staging process, most cancers are classified according to the extent of disease by a numerical system involving stages I through IV.
Stage I usually indicates localized tumor
Stages II and III represent local and regional extension of disease.
Stage IV denotes the presence of distant metastasis.

15. Signs and symptoms Early cancer no symptoms
Change in bowel habits or bladder functions
A sores that do not heal
Unusual bleeding or discharge
Lumps or thickening of breast or other parts of the body
Indigestion or difficulty swallowing
Recent change in wart
Persistent coughing or hoarseness

16. Diagnosis of cancer Self examinations Biopsy
involves histological examination by a pathologist of a piece of tissue.
Imaging techniques
X-rays, CT scan , MRI, ultrasound, bone scans
Laboratory test
Tumor markers(produced by cancer) Example: PSA in patient with Prostate cancers.
alpha fetoprotein in patient with testicular cancer

17. Treatment
Four primary modalities are employed in the approach to cancer treatment:
Surgery (localized therapies)
Radiation (localized therapies)
Chemotherapy
Biological therapy

18. Systemic disease such as leukemia can not treated by localized modality. Chemotherapy ( including hormonal therapy) accesses the systemic circulation and can treat the primary tumor and any metastatic disease.
Solid tumors can be treated by surgery or radiation. But because most patients with cancer have metastatic disease at diagnosis, localized therapies often fail to completely eliminate the cancer.

19. Adjuvant therapy
Adjuvant therapy is defined as the use of systemic agents to eradicate micrometastatic disease following localized modalities such as surgery or radiation or both.

20. Neoadjuvant therapy
Chemotherapy given before surgery or raidotherapy in order to reduce the volume of large primary neoplasm and to determine response to chemotherapy/ hormone therapy in vivo therapy.

21. Purposes of chemotherapy
Cancer chemotherapy may be indicated as a primary, palliative, adjuvant, or neoadjuvant treatment modality.

22. Cell cycle

23. Both cancer cells and normal cells reproduce in a series steps known as the cell cycle.
The first phase is mitosis
M phase (mitosis): In this phase, which lasts only 30 to 60 minutes, during this phase, cell division occur.
G0 phase (resting phase): The cell has not yet started to divide. Some stimulus results in the cell entering the first gap phase (G1).
G1 phase : During this phase, the cell prepares for DNA synthesis by manufacturing necessary enzymes.

24. S phase: In the S phase DNA synthesis occur .It lasts 10 to 20 hours.
The percentage of cells in the S phase can be measured by cytometry and is an indicator of the rate of tumor cell proliferation. Tumors with high percentage of S phase cells are aggressively growing.
Second gap or premitotic G2 phase: during this gap , the cell prepares for mitosis by producing RNA .This phase lasts from 2 to 10 hours.

25. Classification of anticancer drugs
Cell cycle specific agents
1- S phase
A- Antimetabolites
Fluorinated pyrimidines
Fluorouracil
Oral fluoropyrimidines ( Capecitabine)
Cytidine analogs
Cytarabine
Gemcitabine

26. Purines and purine antimetabolites
6- mercaptopurine and 6- thioguanine
Fludarabine monophosphate
Cladribine
Antifolates
Methotrexate
B- Miscellaneous agents
Hydroxyurea
C- alkylating agent
Procarbazine
C- Steroids

27. 2- G2 phase
A- Miscellaneous agents
Bleomycin
B- Microtubule- targeting drugs
Topoisomerase II inhibitors
Etoposide
Teniposide

28. 3- M phase
Microtubule- targeting drugs
Vinca alkaloids
Vincristine
Vinblastine
Vinorelbine
Taxanes
paclitaxel
Docetaxel

29. 4- G1 phase
A- Steroids
B- Miscellaneous agents
Asparaginase

30. Cell cycle phase- non specific agents
1- Alkylating agents
- Classic alkylating agents
(Cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, mechlorethamine)
Nitrosoureas
( Carmustine, lomustine)
- Non classic alkylating agents
( Dacarbazine)

31. 2- Microtubule- targeting drugs
Anthracene derivatives
( doxorubicin, daunorubicin, idarubicin)
3- Miscellaneous agents
( Mitomycin C, dactinomycin)
4- Heavy metal compounds
(cisplatin, carboplatin)