- Senior oncology pharmacist,
Clinical Pharmacy Department, Tanta Oncology Center.
OVERVIEW ― It's important to know that not all cancer treating drugs work in the same way. Some drugs to treat cancer work differently, such as targeted therapy, hormone therapy, and immunotherapy. The information below describes how traditional or standard chemotherapy works ─ See, section "Chemotherapy Drugs".
Chemotherapy drugs target cells at different phases of the cell cycle. Understanding how these drugs work helps doctors predict which drugs are likely to work well together. Cancer cells tend to form new cells more quickly than normal cells and this makes them a better target for chemotherapy drugs. However, chemo-drugs can’t tell the difference between healthy and cancer cells. This means normal cells are damaged along with the cancer cells, and this causes side effects. Each time chemotherapy is given, it means trying to find a balance between killing the cancer cells and sparing the normal cells. The good news is that most normal cells will recover from the effects of chemotherapy over time. However, cancer cells are mutated cells, and they usually do not recover from the effects of chemotherapy drugs. This is why chemo-drugs is good at killing many types of cancer cells.
CHEMOTHERAPY DRUGS
Here we are going to classify the chemo-drugs based on their way of work on cancer cells. We will find that some drugs work in more than one way, and may belong to more than one group. Knowing how the drug works is important in predicting side effects from it. This helps doctors decide which drugs are likely to work well together.
ALKYLATING AGENTS ― Alkylating agents were the first anti-cancer drugs and are the most commonly used agents in chemotherapy today. This chemo-drug group work by preventing the cell from reproducing by damaging its DNA. These drugs work in all phases of the cell cycle and are used to treat many different cancers, including cancers of the lung, breast, and ovary as well as leukemia, lymphoma, Hodgkin disease, multiple myeloma, and sarcoma. Because these drugs are non-specific and damage DNA, they can affect normal cells of the bone marrow which make new blood cells. In rare cases, this can lead to leukemia. The risk of leukemia from alkylating agents is “dose-dependent”, meaning that the risk is small with lower doses, but goes up as the total amount of the drug used gets higher. Examples of alkylating agents (see Table 1).
| Table (1). Examples of alkylating agents |
|---|
| Altretamine, Bendamustine, Busulfan, Carboplatin, Chlorambucil, Cisplatin, Cyclophosphamide Dacarbazine, Ifosfamide, Mechlorethamine, Melphalan, Oxaliplatin, Temozolomide, Thiotepa, Trabectedin.. |
Nitrosoureas, are a group of alkylating agents that have a special action, they can pass to the brain counter to other alkylating agnets listed above. They can enter the brain because they are able to cross the blood-brain barrier. This action makes these drugs useful in treating certain types of brain tumors. Examples of nitrosoureas include carmustine, lomustine and streptozocin...
ANTIMETABOLITES ― Antimetabolites interfere with DNA and RNA by acting as a substitute for the normal building blocks of RNA and DNA. When this happens, the DNA can’t make copies of itself, and a cell can’t reproduce. Thereby they altering the function of enzymes required for cell metabolism and protein synthesis. This group of chemo-drugs are cell cycle specific. They are most effective during the S-phase of cell division because they primarily act upon cells undergoingsynthesis of new DNA for formation of new cells. Antimetabolites are commonly used to treat leukemias, cancers of the breast, ovary, and the intestinal tract, as well as other types of cancer. Examples of antimetabolites (see Table 2).
| Table (2). Examples of antimetabolites |
|---|
| Azacitidine, 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), Capecitabine (Xeloda), Cladribine, Clofarabine, Cytarabine (Ara-C), Decitabine, Floxuridine, Fludarabine, Gemcitabine (Gemzar), Hydroxyurea, Methotrexate, Nelarabine, Pemetrexed (Alimta), Pentostatin, Pralatrexate, Thioguanine, Trifluridine/tipiracil combination.. |
ANTO-TUMOR ANTIBIOTICS ― These drugs are not like the antibiotics used to treat infections. They are cell cycle non-specific. They work by changing the DNA inside cancer cells to keep them from growing and multiplying. Anti-tumor antibiotics include bleomycin, dactinomycin, mitomycin-C and mitoxantrone (also acts as a topoisomerase II inhibitor).
Anthracyclines, are anti-tumor antibiotics that interfere with enzymes involved in copying DNA during the cell cycle. They bind with DNA so it can’t make copies of itself, and a cell can’t reproduce. They are widely used for a variety of cancers. A major concern when giving these drugs is that they can permanently damage the heart if given in high doses. For this reason, lifetime dose limits (also called cumulative dose) are often placed on these drugs. Examples of anthracyclines include daunorubicin, doxorubicin (Adriamycin), doxorubicin liposomal, epirubicin, idarubicin and valrubicin.
PLANT ALKALOIDS ― Plant alkaloids are agents derived from plants. This group of chemo-drugs divided in to: Topoisomerase inhibitors and Mitotic inhibitors.
Topoisomerase inhibitors, they interfere with enzymes called topoisomerase, which help separate the strands of DNA so they can be copied. (Enzymes are proteins that cause chemical reactions in living cells). These drugs act specifically by blocking the ability of a cancer cell to divide and become two cells. Although they act throughout the cell cycle, some are more effective during the S- and M- phases, making these drugs cell cycle specific. Topoisomerase inhibitors are used to treat certain leukemias, as well as lung, ovarian, gastrointestinal, colorectal, and pancreatic cancers. There are two types of Topoisomerase enzymes and inhibitors are grouped according to which type of enzyme they affect (1) Topoisomerase I inhibitors (also called camptothecins) include: irinotecan, irinotecan liposomal and topotecan, (2) Topoisomerase II inhibitors (also called epipodophyllotoxins) include etoposide (VP-16), mitoxantrone (also acts as an anti-tumor antibiotic) and teniposide, (3) Topoisomerase II inhibitors can increase the risk of a second cancer.
Mitotic inhibitors, they work by stopping cells from dividing to form new cells, but can damage cells in all phases by keeping enzymes from making proteins needed for cell reproduction. They are used to treat many different types of cancer including breast, lung, myelomas, lymphomas, and leukemias. These drugs may cause nerve damage, which can limit the amount that can be given. Examples of mitotic inhibitors (include the taxanes and vinca alkaloids). Taxanes include cabazitaxel, docetaxel, paclitaxel. Vinca alkaloids include vinblastine, vincristine, vincristine liposomal and vinorelbine.
CORTICOSTEROIDS ― Often simply called steroids, are natural hormones and hormone-like drugs that are useful in the treatment of many types of cancer, as well as other illnesses. When these drugs are used as part of cancer treatment, they are considered chemotherapy drugs. Steroids are also commonly used to help prevent nausea and vomiting caused by chemo-drugs. They are used before some types of chemo to help prevent severe allergic reactions, too. Examples of corticosteroids include prednisone, methylprednisolone and dexamethasone.
OTHER CHEMOTHERAPY DRUGS ― Some chemotherapy drugs act in slightly different ways and do not fit into any of the other categories. Examples of other chemotherapy drugs (see Table 3).
| Table (3). Examples of other chemotherapy medications |
|---|
| All-trans-retinoic acid, Arsenic trioxide, Asparaginase, Eribulin, Hydroxyurea, Ixabepilone, Mitotane, Omacetaxine, Pegaspargase, Procarbazine, Romidepsin, Vorinostat.. |
REFERENCES
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American Cancer Society (2013). How Chemotherapy Drugs Work. [online] Cancer.org. Available at: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html
Training.seer.cancer.gov. Types of Chemotherapy Drugs | SEER Training. [online] Available at: https://training.seer.cancer.gov/treatment/chemotherapy/types.html