Cancer, its types and anticancer drugs.

Introduction:

Our body is the combination of different cells with different functions and they have ability to divide in controlled manner and produced many cells and destroyed old one according to their need of the body in normal condition but when then body behaves abnormally and cell dividing in rapid form which cannot be stopped then this may lead to tumor and then cancer. Cancer is progressive disease of cell growth in which unstoppable or uncontrollable increase in the mass of cells in terms of numbers, that solid mass is known as tumor and the other liquid cancer also formed maybe in blood or bone marrow. In whole world cancer is up to some extent the leading death cause, its treatment is very complicated and painful and much expensive which involves radiotherapy and the chemotherapy. In chemotherapy the low molecular weight drugs is involved to penetrate and destroy the tumor cells and at some level break its growth but its disadvantage can make major consequences which are bone marrow suppression, hair loss, nausea, vomiting, gastric track lesions and clinical resistance may developed. The cytotoxic cells act on both healthy and tumor cells that why these complications occur. The 1^st time chemotherapy use done by using nitrogen mustards in 1940s, which are very powerful antimetabolites and alkylating agent. Cancer can affect to the every age group but mostly higher age group having chances of it. The body of patient moving to the decline state because all he body nutrition and energy is moving towards the cancerous cells and make the body very much weak by this immune system also become affected and not able to fight with this disease.

 

Cancer and Its Types:

Cancer is a disease characterized by uncontrolled multiplication and spread of abnormal form of the body’s own cells. A normal cells turns into a cancer cells because of one or more mutations in its DNA, which can be acquired or inherited.

Types of Cancer: Our bodies are the combination of trillions of cells. The cells are so tiny we are unable to see them via naked eyes they are only visible under a microscope. Cells are grouped together to form the tissues and organs of our bodies. They are quiet similar but different in some ways because body organs perform very different functions. For example, nerves and muscles do different things, so the cells have different structures. Cancer can be grouped according to the type of cells it starts. There are 5 main types. These are:

1)   Carcinoma – This cancer begins in the skin or in tissues that line or cover internal organs. There are different subtypes, including, 

•       Adenocarcinoma, 
•       Basal cell carcinoma, 
•       Squamous cell carcinoma and 
•       Transitional cell carcinoma

2) Sarcoma – This cancer begins in the connective or supportive tissues such as bone, cartilage, fat, muscle or blood vessels.

3) Leukaemia – This is cancer of the white blood cells. It starts in the bone marrow that is involved in the formation of blood cells.

4) Lymphoma and Myeloma – These cancers begin in the cells of the immune system. 

5) Brain and Spinal cord Cancers – These are known as central nervous system cancers.

 Anticancer Drugs:

Anti-cancer drugs are those medicines which are formulated in order to treat various types of cancer. The usual treatments of cancer are surgery, chemotherapy (treatment with anti-cancer drugs), radiations or some combination of these methods. Anti-cancer drugs are targeted to control and treat various cancers like, breast cancer, cervical cancer, lung cancer, head and neck cancer and ovarian cancer etc. Keep in mind anti-cancer drugs have been designed to slowly slowly show their effects on the cancerous cells and stop their progression by suppressing them via various molecular mechanisms.

Types of Anticancer Drugs: There are two types of anti-cancer drugs.

•   Cell cycle specific (CCS) drugs: These drugs exert their actions selectively on the cycling/proliferating cells, are most effective in hematologic malignancies and in solid tumors in which a relatively large proportion of the cells are proliferating.
•      Cell cycle non-specific (CCNS) drugs: These drugs can kill tumor cells in both cycling and resting phases (although cycling cells are more sensitive). These drugs used in slow growing tumors.

Classification:

•   Antimetabolites: Structurally antimetabolites are related to normal compounds that are found within the cell. Generally they interfere in the availability of precursors of normal purine or pyrimidine nucleotide, either by blocking their synthesis or by competing with them in DNA or RNA synthesis.

Mechanism of Action: These drugs inhibits dihydrofolate reductase, it converts the folate substrate (polyglutamate) first to dihydrofolate (FH2) then to FH4. Methotrexate inhibits dihydrofolate reductase (DHFR)enzyme, so it blocks the DNA, RNA and proteins synthesis.

 Pharmacokinetics:  Antimetabolites is variably absorbed at low doses from the GI track, but it can also be administered by intramuscular, intravenous and intrathecal routes because MTX does not easily penetrate the blood brain barrier. It also distribute to the skin, excretion of parent and 7-OH metabolite occur primarily via urine.

 Clinical Use: It is used to treat leukemia and certain types of cancer of the breast, skin, head and neck, lung, or uterus. Methotrexate is also helpful  to treat the severe psoriasis and rheumatoid arthritis in adults.

 Adverse Effect: Stomatitis, rash, alopecia, myelosuppression. 

 High-dose: renal damage and neurological toxicity.

•       Antibiotics: Antitumor antibiotics own their cytotoxic action primarily to their interaction with DNA, leading to disruption of DNA function.

1.             Doxorubicin and Daunorubicin: Doxorubicin and Daunorubicin are classified as anthracycline antibiotics. Doxorubicin is the hydroxylated derivative of daunorubicin.

Mechanism of Action: Doxorubicin forms complexes with DNA trough G bases in both of the DNA strands and prevents the topoisomerase II activity consequent in cell cycle disruption and cell death, it relaxes DNA super coils by nicking to facilitate DNA replication/ during RNA transcription.

 Pharmacokinetics: These agents must be administered intravenously, because they are inactivated in the GIT. The anthracycline antibiotics binds to plasma protein as well as to other tissues components, where they are distributed. It is mainly eliminated via biliary excretion.

 Clinical Use: Doxorubicin sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer,  acute lymphocytic leukemia, bladder cancer and Kaposi's sarcoma, etc. Sometime it is used along with other chemotherapy agents.

 Adverse Effect: Irreversible, dose-dependent cardiotoxicity is the more serious adverse reaction. Cardiotoxicity apparently results from the generation of the free radicals and lipid peroxidation.

•           Alkylating Agents:

These agents exert their cytotoxic effects by covalently binding to nucleophilic groups which are present on various cell constituents. Alkylation of DNA can be the crucial cytotoxic reaction that is harmful to the tumor.

1.               Ifosfamide: This agent has cytotoxic effects only after formation of its alkylating species, which are produced through hydroxylation via cytochrome P450.

Mechanism of Action: Ifosfamide is first metabolized to hydroxylated intermediates primarily in the liver via CYP 450 system. After that hydroxylated intermediates again metabolized to form the some  other active compounds, phosphoramide mustard and acrolein. The reaction of  phosphoramide mustard with  the DNA would be the cytotoxic action.

 Pharmacokinetics: Ifosfamide is only available in IV form and basically metabolized by CYP450 3A4 and 2B6 iso-enzymes and excreted via renal route.

Clinical Use:   It helps to treat various cancers like testicular cancer by slowing or inhibiting the growth of cancer cells.   

 Adverse Effect: Myelosuppression, Haemorrhagic cystitis, Neurotoxicity, Alopecia and Amenorrhea.     

•        Microtubules Inhibitors:

The mitotic spindles is component of larger, intercellular skeleton (cytoskeleton) that is necessary for the movements of structure that are found in the cytoplasm of  eukaryotic cells.

1.   Vincristine and vinblastine: Vincristine and vinblastine are structurally related to each other and derived from the periwinkle plant.

Mechanism of Action: These drug bind to tubulin and inhibit its polymerization into microtubules, preventing spindle formation in dividing cells and causing arrest at metaphase. This effect become manifest only during mitosis.

 Pharmacokinetics: When these agents are administered via IV injection are responsible for rapid cytotoxic effects and cellular destruction. This is turn, can cause hyperuricemia due to the oxidation of purines that are related from fragmenting DNA molecules. It metabolized through liver.

 Clinical Use: It is used to treat various types of cancer. In order to slow or stop the growth of cancer cells growth these cancer chemotherapy agents are usually given with other chemotherapy agents.

 Adverse Effect: Neurotoxicity, constipation, Myelosuppression and peripheral neuropathy etc.

•        Steroid Hormones:

Tumors that are steroidal hormones sensitive may be either hormone responsive or hormone dependent.

1.   Tamoxifen:

Mechanism of Action: Tamoxifen competes with endogenous estrogen for the estrogen receptors and therefore blocking the proliferation actions of estrogen on mammary epithelium.

 Pharmacokinetics: After oral administration tamoxifen is effective. It is metabolized partially via  the liver. Some of the metabolites have estrogen antagonist activity while other have agonist activity. Unchanged drug metabolism and excretion occur through bile into feces.

 Clinical Use: Tamoxifen is used to treat breast cancer. It is also helpful to decrease the risks of breast cancer in high-risk patients. This medication can block the growth of breast cancer. It acts to distrupt  the effects of estrogen in the breast tissue.

 Adverse Effect: Hot flashes, vomiting, nausea, skin rash, vaginal bleeding, endometrial cancer, effects on vision and thromboembolism.    

•        Topoisomerase Inhibitors:

These agents exert their mechanism of action via inhibition of topoisomerase enzyme.

1.     Camptothecins: Camptothecins are the plant alkaloids, the are originally isolated from Chinese tree camptotheca. 

Mechanism of Action: These drugs are targeted on S-phase and inhibit the activity of topoisomerase I, which is necessary for the DNA replication in the human cells.

 Clinical Use: Other important clinical applications  of camptothecin derivatives are to use as radiation sensitizers or as antiviral agents. The successful development of  camptothecins as antitumor agents shows the importance of topoisomerase I as a target for cancer chemotherapy.

 Adverse Effect: Bone marrow suppression, Neutropenia, Myelosuppression and acute or delayed diarrhea.

Radiotherapy and Chemotherapy Treatment: In radiation therapy waves of energy like light or heat, are used to treat cancers and tumor. Chemotherapy is given as infusion mostly but some chemotherapy pills and capsules also given.

Mechanism of Radiotherapy: These waves break the DNA of cancer cells in such a way that, they disturb their growth and division. In this way, radiation can kill cancer cells, preventing and slowing the spread of the disease.

Mechanism of Chemotherapy: These drugs kill the over growing cells because most of our cells not grown after puberty and there over growth is stopped by chemotherapy agents. 

Common Side Effects: Fatigue, Hair loss, Diarrhea, Skin changes, Nausea and vomiting etc.