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 cancer chemotherapy                                                             

 

Class of chemotherapy drugs  

Chemotherapy is the use of powerful medicines to kill cancer cells. However, all chemotherapy agents do not act the same way. Some chemotherapy drugs affect the behavior of cancer cells without directly attacking them; and some directly attack the DNA of the cells, preventing them from multiplying. Others do not act directly; they target the molecular abnormality in certain types of cancer. Depending on their biochemical mode of action, chemotherapy drugs (also called antineoplastic or cytotoxic drugs which means toxic to cells or cell-killing) are grouped into different therapeutic classes: Alkylating agents (also called DNA damaging agents), anti-metabolites, plant alkaloids and terpenoids, podophyllotoxin, taxanes, topoisomerase inhibitors, antitumour antibiotics, hormones, and monoclonal antibodies.   

Alkylating agents (also called DNA damaging agents): alkylating agents are molecules that form chemical bonds. In other words, they are able to establish covalent bonds with the DNA of all cells (normal or cancerous), but mainly cells that reproduce rapidly which is the main characteristic of cancer cells. Alkylating agents stop tumor growth by establishing a cross-linking in the double helix in the DNA of cancer cells and, unfortunately, some normal cells that multiply rapidly. This process prevents the cells from replicating their DNA, and become unable to divide.   

Alkylating agents include several drugs, the most common are: cisplatin, carboplatin (Paraplatin), ifosfamide, chlorambucil, busulfan, and thiotepa. 

Anti-metabolites: These anticancer agents work by inhibiting the synthesis of nucleic acids (DNA, RNA), a necessary process in cell multiplication. In nature, cancer cells divide more frequently than normal cells; and therefore any halt in cell division affect cancer cells more than healthy cells. Antimetabolites fight cancer by interfering with DNA of cancerous cells, which stops or slows the growth of the tumor. 

The antimetabolites are among the oldest chemical agents used in chemotherapy. It is thought that they have been used in the fight against cancer since the late 1940s. Today, they are widely prescribed for the treatment of cancers in children and adults. Depending on their therapeutic action, anti-metabolites are divided into three groups:  

  • Pyrimidine analogues - those molecules are found mainly in nitrogenous bases making up the molecules of DNA and RNA. Pyrimidines and purines (see antipurine below) are nucleotides that form the building blocks of nucleic acids. One of the anti pyrimidines agents is 5-fluorouracil (5FU), a drug used in the treatment of many cancers principally colorectal cancer and pancreatic cancer. 
  • Purine analogues - they are substances that inhibit enzyme which are very active during cell replication: DNA polymerase, DNA primase and DNA ligase I. Among drugs that are classed purine analogues include Fludarabine (fludarabine phosphate or Fludara) , a chemotherapeutic drug used to treat chronic lymphocytic leukemia.  
  • Antifolates – chemotherapy drugs act in the action of synthesis of folate. In other words, antifolates impair the function of folic acids, substances essential for the biosynthesis of nucleic acids. One of the most common of antifolates is methotrexate (Trexall, Rheumatrex); i t acts by inhibiting dihydrofolate reductase, an enzyme essential for synthesis of purines and pyrimidines.  

Plant alkaloids and terpenoids: a lkaloids are organic substances of vegetable origin (caffeine, mescaline, nicotine, caffeine, etc...) that have therapeutic properties. They are used in the production of cancer drugs. The alkaloids act by preventing the formation of (cellular) spindle, the structure which allows the chromatic separation of chromosomes during cell division (mitosis or division of a "mother cell" into two "daughter cells"). The process causes the cells to remain blocked at the stage of mitosis and unable to divide. 

The most common alkaloids include vincristine, vinblastine, vinorelbine, paclitaxel and docetaxel. They are used to treat a variety of cancers, including but not limited to:  

 

  • lung cancer 
  • breast cancer  
  • testicular cancer  
  • acute lymphoblastic leukemia  
  • Hodgkin's Disease 
  • non-Hodgkin's lymphoma 
  • neuroblastoma  
  • Wilms Tumor. 

Taxanes: the taxanes are a class of drugs widely used in chemotherapy to fight cancer. Their main function is to halt cell division. Cancer cells multiply in an anarchic way; by blocking cell division, the taxanes make it difficult for the tumor to grow.  

Although can be used in the treatment of other cancerous conditions, the taxanes are used mainly to treat advanced stages of breast cancer, lung cancer and metastatic ovarian cancers. The taxanes include paclitaxel and docetaxel.  

Topoisomerase inhibitors: DNA topoisomerases are essential enzymes that maintain the topology of DNA: replication, transcription and recombination. They control and modify the topological states of cells DNA. There are two forms of DNA topoisomerases: topoisomerase I, which cut and link complementary rings of single-stranded DNA into double-stranded rings; and topoisomerase II, which cuts both the two strands of DNA and link them in a different conformation after modification of its torsion. 

The topoisomerase inhibitors interfere with both transcription and cell replication by inhibiting the relegation of DNA fragments. Among this class of chemotherapy drugs include amsacrine, anthracyclines, camptothecin derivative (Irinotecan), and epipodophyllotoxin derivatives (etoposide and teniposide). The topoisomerase inhibitors are used to treat several types of cancers including colorectal cancers that have been treated unsuccessfully with 5-fluoro-uracil/acid folic (folinic acid combined with 5-fluorouracil). 

Antitumour antibiotics: a ntitumour antibiotics are a class of chemotherapy drugs used to treat certain malignancies such as acute myeloid leukemia, breast cancer, and non-small cell lung cancer. These drugs act by preventing cell division in both cancerous cells and healthy cells that multiply rapidly. The most common antitumour antibiotics include: 

  • Aclarubicin 
  • Bleomycin 
  • Dactinomycin 
  • Daunorubicin 
  • Doxorubicin 
  • Epirubicin 
  • Mythramycin 
  • Mitomycin 
  • Zorubicin. 

Hormones: hormone-dependent or hormone sensitive cancers (prostate cancer and breast cancer for example) feed on hormones; their cells need hormones to grow and reproduce. For example, estrogen produced by the ovaries may contribute to the development of certain cancers of breast and uterus; androgens, hormones produced by the testes, can be involved in the development of prostate cancer. Hormone therapy is used to block hormonal stimulation, thus stopping or slowing tumor growth. 

In the fight against cancer, hormone can act different manner; for example:  

  • In the treatment of prostate cancer, finasteride selectively inhibits 5-alpha reductase, an enzyme that catalyzes the conversion of testosterone into dihydrotestosterone (DHT). This causes a discontinuity of production of 5-hydroxytestosterone, which results in inhibition of cell growth of prostate cancer. 
  • Aromatase inhibitors and tamoxifen are used to treat breast cancers that are either ER-positive (ER or estrogen receptor) or PR-positive (PR or progesterone receptor). These drugs act by inhibiting the production of estrogen and/or progesterone. 
  • Gonadotropin-releasing hormone agonists (GnRH agonist) are used to treat hormonally sensitive cancers such as prostate cancer and breast cancer. GnRH agonists such as Goserelin work by impairing the function of the hypophysis (also called pituitary gland), a pea-sized gland located in the frontal portion of your brain that controls the functions of the other endocrine glands.  

 Monoclonal antibodies: Our body has a natural defense called immune system. One of the properties of the immune system is to produce antibodies against bacteria, viruses and other pathogenic attacks. Having a weak immune system, the body becomes a gateway to several illnesses. To boost weakened immune system, scientists have produced industrially very pure antibodies called monoclonal antibodies. Monoclonal antibodies directed against antigens carried by tumor cells to specifically destroy them.  

Unlike other chemotherapy drugs which attack both healthy cells and cancer cells, monoclonal antibodies primarily target diseased cells and causing fewer side effects. In other words, monoclonal antibodies are substances that deprive cancer cells of their growth opportunities, and cause them to commit suicide. Among drugs classed as monoclonal antibodies include:  

  • Herceptin, used in the treatment of breast cancer    
  • Rituximab, used to treat lymphoma