ANTICANCER DRUGS

 

ANTICANCER DRUGS

PREPARED BY MR. ABHIJIT DAS

CANCER

·       One defining feature of cancer is the rapid formation of abnormal cells that grow beyond their usual boundaries, and which can then invade adjoining parts of the body and spread to other organs.

·       Cancer is the second leading cause of death globally (9.6 million deaths in 2018).

·       Other terms used for cancer are malignant tumors and neoplasm.

Ø  "neo-" = new

Ø  "plasm" = growth or formation.

Ø  So, Neoplasia refers to abnormal and uncontrolled cell growth, which leads to tumors or cancers.

 

WHAT CAUSES CANCER?

Cancer is the result of the interaction between a person’s genetic factors and three categories of external agents (carcinogens), including:

1.     Physical carcinogens, such as ultraviolet radiation

2.     Chemical carcinogens, such as components of tobacco smoke, alcohol.

3.     Biological carcinogens, such as infections from certain viruses, bacteria, or parasites.

 

CLASSIFICATION OF ANTICANCER DRUGS

1. Alkylating Agents
• Cyclophosphamide
• Ifosfamide
• Mechlorethamine
• Thiotepa
• Busulfam
• Dacarbazine
2. Antimetabolites
• Folate Antagonist
• Methotrexate
• Pemetrexed
• Purine Antagonists
• 6-Mercaptopurine
• 6-Thioguanine
• Azathioprine
• fludarabine
• Pyrimidine Antagonists
• 5-Fluorouracil
• Cytarabine
3. Vinca Alkaloids
• Vincristine
• Vinblastine
• Vinorelbine
4. Taxanes
• Paclitaxel
• Docetaxel
• Cabazitaxel
5. Epipodophyllotoxins
• Etoposide
• Teniposide

 

ANTIMETABOLITES

These drugs generally inhibit purine or pyrimidine synthesis in the cancer cells. So, no nucleotide is synthesized and no DNA or RNA is formed.

 

FOLATE ANTAGONIST:

METHOTREXATE (MTX)

MOA:

Methotrexate is an antifolate agent. It inhibits dihydrofolate reductase (DHFR), an enzyme involved in the conversion of dihydrofolate to tetrahydrofolate. Tetrahydrofolate is essential for the synthesis of purines and pyrimidines, which are necessary for DNA and RNA synthesis. By blocking this pathway, methotrexate interferes with the replication and function of rapidly dividing cells, including cancer cells.

ADVERSE EFFECTS:

• Myelosuppression: Anemia, leukopenia, thrombocytopenia
• Gastrointestinal: Nausea, vomiting, diarrhea, mucositis
• Hepatotoxicity: Elevated liver enzymes, liver fibrosis, cirrhosis
• Nephrotoxicity: Renal dysfunction, elevated serum creatinine
• Pulmonary Toxicity: Pneumonitis, pulmonary fibrosis
• Neurotoxicity: Headaches, dizziness, seizures (high doses)

[NOTE: Fibrosis is a medical condition characterized by the formation of excess fibrous connective tissue in an organ or tissue in response to injury, damage, or inflammation.]

USES:

• Acute lymphoblastic leukemia (ALL) [A rapidly progressing cancer of the bone marrow characterized by the overproduction of immature lymphocytes.]
• Non-Hodgkin’s lymphoma [a cancer that originates in the lymphatic system, characterized by the proliferation of abnormal lymphocytes, which are a type of white blood cell, leading to the formation of tumors in lymph nodes and other lymphoid tissues]
• Breast cancer
• Osteosarcoma [Bone Cancer]

 

PURINE ANTAGONISTS:

6-MERCAPTOPURINE (6-MP)

MECHANISM OF ACTION (MOA):

6-Mercaptopurine (6-MP) is a purine analog that inhibits the synthesis of purine nucleotides. It interferes with DNA synthesis by being incorporated into the nucleic acids, leading to the inhibition of the proliferation of rapidly dividing cells, such as cancer cells and white blood cells.

ADVERSE EFFECTS:

1. Bone marrow suppression
2. Hepatotoxicity
3. Nausea and vomiting

USES:

1. Acute lymphoblastic leukemia (ALL)
2. Inflammatory bowel disease (IBD)

 

6-THIOGUANINE

Mechanism of Action (MOA): 6-Thioguanine is a guanine analog that is incorporated into DNA, disrupting their synthesis, which inhibits the growth of rapidly dividing cells.

Adverse Effects:

1. Bone marrow suppression
2. Hepatotoxicity
3. Nausea and vomiting

Uses:

1. Acute myeloid leukemia (AML)
2. Chronic myeloid leukemia (CML)

[NOTE:
Myeloid leukemia (AML): A type of cancer where the bone marrow produces abnormal myeloblasts, red blood cells, or platelets.

Myeloblast: An immature white blood cell found in the bone marrow that can develop into a type of white blood cell called a granulocyte.]

 

PYRIMIDINE ANTAGONISTS:

5-FLUOROURACIL

MECHANISM OF ACTION (MOA):

5-Fluorouracil is an uracil analog that interferes with the synthesis of DNA and RNA, ultimately leading to cell death.

ADVERSE EFFECTS:

1. Myelosuppression
2. Gastrointestinal toxicity

USES:

1. Colorectal cancer
2. Breast cancer

 

CYTARABINE

MECHANISM OF ACTION (MOA):

Cytarabine, a cytidine analog, interferes with DNA synthesis, ultimately leading to cell death.

ADVERSE EFFECTS:

1. Myelosuppression
2. Nausea and vomiting

USES:

1. Acute myeloid leukemia (AML)
2. Non-Hodgkin lymphoma

 

ALKYLATING AGENTS

MOA:

Alkylating agents work by adding alkyl groups to DNA, leading to DNA strand breakage. This prevents DNA replication, ultimately leading to cell death.

ADVERSE EFFECTS:

• Myelosuppression: Decreased production of blood cells, leading to anemia, leukopenia, and thrombocytopenia.
• Gastrointestinal: Nausea, vomiting, and diarrhea.
• Cardiotoxicity: Heart damage, especially with high doses.
• Immunosuppression: Increased susceptibility to infections.

USES:

• Cancer Treatment:
• Leukemias (acute lymphocytic leukemia, chronic lymphocytic leukemia)
• Breast cancer
• Ovarian cancer
• Non-Cancer Conditions:
• Autoimmune diseases (e.g., rheumatoid arthritis)

 

VINCA ALKALOIDS

VINCRISTINE

MECHANISM OF ACTION (MOA):

Inhibits microtubule formation, disrupting mitosis and cell division.

ADVERSE EFFECTS:

1. Peripheral neuropathy
2. Constipation

USES:

1. Various cancers, including leukemia and lymphoma
2. Pediatric tumors, such as neuroblastoma

VINBLASTINE

MECHANISM OF ACTION (MOA):

Inhibits microtubule formation, disrupting mitosis and cell division.

ADVERSE EFFECTS:

1. Bone marrow suppression
2. Hair loss

USES:

1. Hodgkin's lymphoma
2. Testicular cancer

 

 

 

 

SOME IMPORTANT TERMS RELATED TO CANCER

TUMOR: A mass formed when normal cells grow uncontrollably. A tumor can be benign (noncancerous) or malignant (cancerous, meaning it can spread to other parts of the body).

BENIGN: It refers to a tumor that is noncerous because the tumor does not spread to other parts of the body.

MALIGNANT: It refers to a tumor that is cancerous because the tumor can spread to other parts of the body.

CHEMOTHERAPY: The use of drugs to kill cancer cells.

MYELOSUPRESSION: Myelosuppression means suppression (reduction) of bone marrow activity.