One of the three modalities of cancer treatment, chemotherapy is understood as the conventional line of treatment for a series of different types of cancers. The primary aim of chemotherapy drugs is to inhibit cell proliferation and the multiplication of tumors thereby decreasing the possibility of cancer metastasis. Chemotherapy employs drugs that are cytotoxic which essentially means that it not only kills the malignant cancer cells but also the healthy cells of the body. Since chemotherapy’s primary aim is to inhibit cell growth, the drugs in this line of treatment target different phases of the cell cycle and thereby hinders the cell reproduction process at different stages. Each chemotherapy drug serves a specific purpose and these drugs are usually administered in combination to improve the response rates of the line of treatment.
Alkylating Agents
Alkylating agents are a set of drugs that are able to exert their action irrespective of the phase of the cell cycle. They are also commonly referred to as non-cell cycle specific drugs. Since these drugs directly interfere with the DNA, alkylating chemicals can stop a cell from rapidly dividing by producing aberrant base pairing, DNA strand breakage or cross linking of the DNA strands. These sets of drugs work by adding an alkyl group to the base of the DNA molecule, which prevents the strands of the double helix from linking as they should. This then results in the breakage of the DNA strands, interfering with the ability of the cancer cell to proliferate and ultimately results in the death of the cancer cell.
Since alkylating agents are potent at different stages of the cell cycle, they are effective for treating a wide range of cancers. While they may be most effective for slow growing cancers such as leukemia and solid tumors, they are also commonly employed in the treatment of breast, ovarian, prostate and lung cancers. Due to the fact that alkylating agents affect all cells that are dividing, they are also toxic to the healthy cells of the body especially those of the gastrointestinal tract, bone marrow, testicles and ovaries.
Some of the alkylating agents that are commonly used include –
- Mustard Gas Derivatives – Mechlorethamine,Cyclophosphamide, Chlorambucil, Melphalan, and Ifosfamide.
- Ethylenimines: Thiotepa and Hexamethylmelamine.
- Alkyl Sulfonates – Busulfan.
- Hydrazines and Triazines – Altretamine, Procarbazine, Dacarbazine and Temozolomide.
- Nitrosoureas – Carmustine, Lomustine and Streptozocin.
- Metal salts: Carboplatin and Oxaliplatin.
Antimetabolites
One of the oldest sets of chemotherapy drugs, antimetabolites operate by mimicking molecular cancer cells that need to replicate their genetic information and interfere with their ability to replicate. These drugs interrupt with the enzymes and the reactions that are necessary for DNA synthesis.
They impact the DNA synthesis by acting as a substitute for the actual metabolites that are used for the normal metabolism of the body. Stated differently, antimetabolites imitate the nutrients necessary for cellular growth, leading the cell to mistakenly absorb them and thereby starve to death. Antimetabolites hinder the cells from carrying out vital functions thereby ensuring that these cells are unable to proliferate and survive.
The subtypes of antimetabolite agents include –
- Antifolates – Pemetrexed and Pralatrexate.
- Pyrimidine Analogs – 5-Fluorouracil, Capecitabine, Cytarabine.
- Purine Analogs – Fludarabine, Clabridine, Pentostatin.
- Ribonucleotide Reductase Inhibitors – Hydroxyurea
Plant Alkaloids and Natural Products
Also referred to as Mitotic Inhibitors, Plant Alkaloids are derived from natural products such as plants. They operate by stopping cells from dividing to form new cells but can affect cells in all phases by inhibiting enzymes from making proteins that are needed for cell reproduction. The vinca alkaloids are made from Also referred to as Mitotic Inhibitors, Plant Alkaloids are derived from natural products such as plants. They operate by stopping cells from dividing to form new cells but can affect cells in all phases by inhibiting enzymes from making proteins that are needed for cell reproduction. The Vinca alkaloids are made from the periwinkle plant ( catharanthus rosea) and the taxanes are made from the bark of the Pacific Yew Tree ( taxus). The vinca alkaloids and taxanes are also commonly referred to as antimicrotubule agents. The Podophyllotoxins which are another type of plant alkaloids are derived from the May apple plant while Campthothecans are derived from the Asian Happy Tree (Campthotheca acuminata). Both Podophyllotoxins and Campthothecans are commonly known as topoisomerase inhibitors which are also a set of different types of chemotherapy. Plant alkaloids are cell specific which essentially means that they target the different phases of the cell cycle.
Antitumor Antibiotics
Antitumor Antibiotics are sets of drugs that are derived from the Streptomyces bacteria. Antitumor antibiotics work by changing the DNA inside the cancer cells to keep them from growing and multiplying. Anthracyclines are drugs that belong to this category and they function by interfering with the enzymes that are involved in copying DNA during the cell cycle. Anthracyclines bind with the DNA which allows it to then make several copies of itself and inhibit cell reproduction. These drugs are cell cycle specific and target a cell at different stages of the cell cycle.
Some of the different antitumor antibiotics that are commonly used to treat a wide range of cancers include –
- Anthracyclines – Doxorubicin, Daunorubicin, Epirubicin, Mitoxantrone and Idarubicin.
- Chromomycin – Dactinomycin and Plicamycin.
- Miscellaneous – Mitomycin and Bleomycin.
Key Terms To Know
Adjuvant Chemotherapy
Adjuvant chemotherapy refers to the line of treatment that is used following the primary therapy to get rid of any residual cancer cells and lower the risk of cancer recurrence. If a tumor is removed after surgery then there is always a possibility that a small number of cancer cells may have spread into the lymphatic system or the adjoining organs. Although the number of these cancer cells may be so small that they often go undetected. They are known as micrometastases and administering chemotherapy after surgery significantly reduces the chances of these cancer cells from forming recurrent tumors or metastasizing to other parts of the body.
Summary
Chemotherapy drugs are cell specific and target different phases of the cell cycle to inhibit its activity. Alkylating agents, antimetabolites, plant alkaloids and antitumor antibiotics are often administered to a patient in combinations to improve the outcomes of cancer.
