10.anticancer drugs

BYBY

Dr. Dr. SAMINATHAN KAYAROHANAMSAMINATHAN KAYAROHANAM

M.PHARM, M.B.A, PhDM.PHARM, M.B.A, PhD

ANTICANCER DRUGS

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NUM CONTENT SLIDE

1 INTRODUCTION/DIFINTION 42 EPIDEMIOLOGY OF CANCER 53 RISK FACTORS 64 CHARACTERISTIC OF CANCER 75 THE SEVEN WARNING SIGNS OF CANCER 86 CANCER TYPES 97 CELL CYCLE 108 CARCINOGENESIS 119 FORMATION OF MALIGNAT CELL BY MUTATION 12

10 TREATMENT OPTIONS OF CANCER 1311 DIAGNOSIS OF CANCER 1412 CELL CYCLE SPECIFIC /NON- SPECIFIC DUGS 1513 ANTI CANCER DRUG CLASSIFICATION 16-1914 CHEMOTHERAPEUTIC DRUGS AFFECTING RNA /DNA PRECURSORS 2015 COMPARISON OF MYELOSUPPRESSIVE POTENTIAL OF

CHEMOTHERAPEUTIC DRUGS21

16 MECHANISAM OF ANTICANCER DRUGS 2217 TOXIC EFFECTS OF ANTI CANCER DRUGS 4018 CONCLUSION. 42

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LEARNING OUTCOME

1. Define cancer and Describe cell cycle.

2. Able to demonstrate the risk factor, character , diagnosis and treatment of cancer

3. Able to understand the warning signs of cancer.

4. List the anti cancer drug classification.

5. Abele to demonstrate the mechanism of cancer drugs.

6. Describe the toxic effects of anti cancer drugs.

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Cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs. This process is referred to as metastasis. Metastases are the major cause of death from cancer. (WHO)

Cancer known medically as a malignant neoplasm, is a broad group of diseases involving unregulated cell growth. In cancer, cellsdivide and grow uncontrollably, forming malignant tumors, and invading nearby parts of the body. The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream. Not all tumors are cancerous; benign tumors do not invade neighboring tissues and do not spread throughout the body. There are over 200 different known cancers that affect humans.

1. INTRODUCTION/DIFINTION

Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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2. EPIDEMIOLOGY OF CANCER


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3. RISK FACTORS

1.Tobacco

2.Sunlight

3.Ionizing radiation

4.Certain chemicals and other substances

5.Some viruses and bacteria

6.Certain hormones

7.Family history of cancer

8.Alcohol

9.Poor diet, lack of physical activity, or being overweight


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Cancer arises as a result of a series of genetic and epigenetic changes, the main genetic lesions being:

• inactivation of tumour suppressor genes • the activation of oncogenes (mutation of the normal genes controlling

cell division and other processes).

Cancer cells have four characteristics that distinguish them from normal cells:

• uncontrolled proliferation • loss of function because of lack of capacity to differentiate • invasiveness • the ability to metastasise.

Cancer cells have uncontrolled proliferation because of changes in: • growth factors and/or their receptors • intracellular signalling pathways, particularly those controlling the cell

cycle and apoptosis • telomerase expression • tumour-related angiogenesis

4. CHARACTERISTIC OF CANCER


5. THE SEVEN WARNING SIGNS OF CANCER

The American Cancer Society uses the wordC-A-U-T-I-O-N to help recognize the seven early signs of cancer:

1.Change in bowel or bladder habits2.A sore that does not heal3.Unusual bleeding or discharge4.Thickening or lump in the breast, testicles, or elsewhere5.Indigestion or difficulty swallowing6.Obvious change in the size, color, shape, or thickness of a wart, mole, or mouth sore7.Nagging cough or hoarseness8


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categorized based on the functions/locations of the cells from which they originate:

Carcinoma: a tumor derived from epithelial cells, those cells that line the surface of our skin and organs (80-90% of all cancer cases reported)Sarcoma: a tumor derived from muscle, bone, cartilage, fat or connective tissues. Leukemia: a cancer derived from white blood cells or their precursors. Lymphoma: a cancer of bone marrow derived cells that affects the lymphatic system. Myelomas: a cancer involving the white blood cells responsible for the production of antibodies (B lymphocytes)

6. CANCER TYPES


Go – Resting phaseRestriction checkpoint

8hrs or more

6-8 hrs

2-5 hrs

7. CELL CYCLE

10 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

Normal Cell

DNA Damage

Mutations in the genome of somatic cells

Alteration of genes that regulates apoptosis

Expression of altered gene productsLoss of regulatory gene product

MALIGNANT NEOPLASM

Activation of growth promoting

oncogene

Inactivation of cancer suppressor genes

Acquired (environmental DNA damaging agents)

ChemicalsRadiationviruses

Successful DNA repair

Failure of DNA repair

8. CARCINOGENESIS

•Clonal expansion•Additional mutations•Heterogeneity

11Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

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9.FORMATION OF MALIGNAT CELL BY MUTATION


10. TREATMENT OPTIONS OF CANCER

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1. Surgery:

before 1955

2.Radiotherapy:

1955~1965

3. Chemotherapy:

after 1965

4. Immunotherapy

5. Gene therapy


11. DIAGNOSIS OF CANCER Biopsy - involves histological examination by a

pathologist of a piece of tissue.

Imaging techniques – • CT scan, • MRI, • UTZ

Laboratory test

Tumor markers(produced by cancer)Example:

CA15-3 - Breast cancer.CA19-9 - Gastrointestinal tumours.CA-125 - Ovarian cancers.PSA - Prostate cancers.

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12.CELL CYCLE SPECIFIC /NON- SPECIFIC DUGS

CON…


13.ANTI CANCER DRUG CLASSIFICATION


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13.ANTI CANCER DRUG CLASSIFICATION WITH CLASS /TYPE

CON…


18CON…


14.CHEMOTHERAPEUTIC DRUGS AFFECTING RNA /DNA PRECURSORS.


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15. COMPARISON OF MYELOSUPPRESSIVE POTENTIAL OF CHEMOTHERAPEUTIC DRUGS


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Methotrexate potently inhibits Dihydrofolate reductase (DHFR).

This leads to decreased production of compounds adenine, guanine and thymidine and the amino acids methionine and serine, depletion of thymidine.

Finally depressed DNA, RNA, and protein synthesis and, ultimately, to cell death.

FH2 = dihydrofolate; FH4 = tetrahydrofolate; dTMP = deoxythymidine monophosphate; dUMP = deoxyuridine mono phosphate.

16.1 MECHANISM OF ACTION OF METHOTREXATE


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6-Mercaptopurine penetrates target cells and be converted to the nucleotide analog.

This leads to inhibit the first step of de novo purine-ring biosynthesis

This results in non-functional RNA and DNA.

16.2 MECHANISM OF ACTION OF 6-MERCAPTOPURINE


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5-FU = 5-fluorouracil; 5-FUR = 5-fluorouridine; 5-FUMP = 5-fluorouridine monophosphate; 5-FUDP = 5-fluorouridine diphosphate; 5-FUTP = 5-fluorouridine triphosphate; dUMP = deoxyuridine monophosphate; dTMP = deoxythymidine monophosphate. 5-FdUMP = 5-fluorodeoxyuridine monophosphate.

16.3 MECHANISM OF ACTION OF 5-FLUOROURACIL

5-Fluorouracil competes with deoxyuridine monophosphate for thymidylate synthase and reduce the thymidine.

DNA synthesis decreases due to lack of thymidine, leading to imbalanced cell growth.


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Gemcitabine inhibits DNA synthesis by being incorporated into sites in the growing strand that ordinarily would contain cytosine.

Gemcitabine diphosphate inhibits ribonucleotide reductase, which is responsible for the generation of deoxynucleoside triphosphates required for DNA synthesis.

16.4 MECHANISM OF ACTION OF GEMCITABINE


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Doxorubicin and daunorubicin bind to the sugar-phosphate backbone of DNA. This causes local uncoiling. Which leads to blocks DNA & RNA synthesis and catalyzed breakage supercoiled DNA strands, causing irreparable breaks.

Catalyzes the reduction of free radicals. These in turn reduce molecular O2, producing superoxide ions and hydrogen peroxide, which mediate single-strand scission of DNA.

16.5 MECHANISM OF ACTION OF DOXORUBICIN AND DAUNORUBICIN


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A DNA-bleomycin-Fe2+ complex appears to undergo oxidation to bleomycin-Fe3+.

The liberated electrons react with oxygen to form superoxide or hydroxyl radicals, which in turn attack the phosphodiester bonds of DNA, resulting in strand breakage and chromosomal aberrations.

16. 6 MECHANISM OF ACTION OF BLEOMYCIN


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Mechlorethamine is alkylates the N7 nitrogen of a guanine residue in one or both strands of a DNA molecule This alkylation leads to cross-linkages between guanine residues in the DNA chains and/or depurination, thus facilitating DNA strand breakage.

Alkylation can also cause miscoding mutations.

16. 7 MECHANISM OF ACTION OF MECHLORETHAMINE


16. 8 MECHANISM OF ACTION OF VINCA ALKALOIDS


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16. 9 MECHANISM OF ACTION OF PACLITAXEL


16. 10 MECHANISM OF ACTION OF ANTIESTROGEN


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Flutamide,nilutamide and bicalutamide are synthetic, nonsteroidal antiandrogens used in the treatment of prostate cancer.

Estrogens, such as ethinyl estradiol or diethylstilbestrol, had been used in the treatment of prostatic cancer. However, they have been largely replaced by the GnRH analogs because of fewer adverse effects.

Estrogens inhibit the growth of prostatic tissue by blocking the production of LH, thereby decreasing the synthesis of androgens in the testis.

16. 11 MECHANISM OF ACTION OF ESTROGENS IN PROSTATIC CANCER


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Tamoxifen binds to the estrogen receptor and the complex fails to induce estrogen-responsive genes, and RNA synthesis does not ensue.

The result is depletion (down-regulation) of estrogen receptors, and the growth-promoting effects of the natural hormone and other growth factors are suppressed.

The action of tamoxifen is not related to any specific phase of the cell cycle.

16. 12 MECHANISM OF ACTION OF TAMOXIFEN


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Normal unwinding of double helix

Irinotecan and topotecan are inhibit

the unwinding of double helix

Con…

16. 13 MECHANISM OF ACTION OF IRINOTECAN &TOPOTECAN


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Irinotecan and topotecan are semisynthetic derivatives.These drugs are S-phase specific. They inhibit topoisomerase I, which is essential for the replication of DNA in human cells.

16. 13 MECHANISM OF ACTION OF IRINOTECAN &TOPOTECAN


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16. 14 MECHANISM OF ACTION OF ETOPOSIDE &TENIPOSIDE

Normal catalytic cycle of topoisonerase which is inhibited by the Etoposide and its analog, teniposide

Con…


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Etoposide and its analog, teniposide are semisynthetic derivatives of the plant alkaloid, They block cells in the late S to G2 phase of the cell cycle.

Their major target is topoisomerase II. Binding of the drugs to the enzyme-DNA complex results in persistence of the transient, cleavable form of the complex and, thus, renders it susceptible to irreversible double-strand breaks

16. 14 MECHANISM OF ACTION OF ETOPOSIDE &TENIPOSIDE


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16. 15 MECHANISM OF ACTION OF L-ASPARAGINASE


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•Bone marrow toxicity (myelosuppression) with decreased leucocyte production and thus decreased resistance to infection

•Impaired wound healing

•Loss of hair (alopecia)

•Damage to gastrointestinal epithelium

•Depression of growth in children

•Sterility

•Teratogenicity.

17.TOXIC EFFECTS OF ANTI CANCER DRUGS


Acute toxicity Vomiting Allergic reactions Arrhythmias

Delayed effects Mucositis Alopecia Bone marrow suppression

Chronic toxicities Heart Kidney Liver Lungs


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18.CONCLUSIONEvery year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable.

Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle.

The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc.

Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups.


10.anticancer drugs

Health & Medicine

cancer cells

diagnosis of cancer

treatment of cancer

cancer types

mechanism of cancer

warning signs of cancer

epidemiology of cancer

characteristic of cancer