In her latest cancer potions class, Prof Carol-Ann Benn educates us on what drugs are used to treat cancer and how they work.
This might be a pass-fail class for anyone who is exposed to the word cancer. How the oncologist determines what cytotoxic drugs and combinations can be used is critical because no one wants this treatment. Yes, everybody wants to avoid chemotherapy. So, to help you understand and pass this potion class I’ll explain what chemotherapy is and how it works. This is an equivalent to a first-year Hogwarts’ potions class. Don’t fail, Prof Snape is the examiner.
Basic cell biology
Chemotherapy drugs can be given as an individual or as a combination to achieve a desired effect. The chemical composition of these drugs is such that are successful in killing cancer cells. The stressors that most people have around how they work is that they kill normal cells as well.
So, let’s understand why and how this happens. Remember the cancer’s aim is to kill all your cells. An important start to the potions class is to understand that not all drugs work the same way.
Basic cell biology (the building blocks) before understanding how drugs work involves understanding that a cell has a cell membrane which is its protective wall, and inside the cell house is the DNA (the brain); the RNA (the brain’s central control board).
To start the class, remember that basic cell biology is about all cells going through a process to become a functioning mature cell. These phases are known as the cell cycle. Chemotherapy drugs target different phases of the cell cycle. This is why drugs are given at certain doses and at certain times to coincide with the cell phases.
Understanding that cancer cells divide faster than normal cells makes them easier to target, and because normal cells divide as well, chemotherapy drugs also affect the normal dividing cells.
A yin yang recipe
So, chemo is a bit like a yin yang recipe of trying to obtain that balance between killing cancer cells (to cure and control) and not killing normal cells (fewer side effects). Why is this okay to do? Normal cells can usually recover and cancers being abnormal cells can usually not recover.
As with any class, particularly a chemistry class, the structure of the drugs and how they relate to other drugs as well as how they work (some drugs work in different ways, with more than one having actions in different phases) is a bit like using the same chemistry components and equations in different alchemy experiments. By understanding how the drugs work in principle, this gives us an understanding of which ones work together for the best effects and what the different side effects are.
Alkylating agents
The first group are the alkylating agents. They work by preventing the cell from making a copy of itself; they do this by damaging the cell’s DNA.
To do that they are able to work in all phases of the cell cycle and can be used to treat many different types of cancer (from breast and lung to lymphomas and blood cancers).
So, because they affect the cell DNA they can affect the cells of the bone marrow which explains why the new blood cell counts drop (white and red cells) and why they can cause leukaemias five to 10 years post-treatment. Please note: this is uncommon and dependent on higher dosages of drugs.
You may recognise the platinum chemotherapeutics (cisplatin and carboplatin) and the drug cyclophosphamide as part of this group. There is a sub-class of these that can cross the blood-brain barrier called nitrosoureas, although they aren’t commonly used to treat breast cancer.
Antimetabolites
This group of oncology drugs interfere with the DNA and RNA by acting as a substitute for the normal building blocks of RNA and DNA.
This means that the DNA can’t copy itself and the cell can’t reproduce.
These drugs are used to treat breast cancer, ovarian cancer, some GIT malignancies, leukaemia and a variety of other cancers. Names that you might recognise are 5-fluorouracil, capecitabine gemcitabine, methotrexate and nelarabine.
Anti-tumour antibiotics
These drugs aren’t like the antibiotics used to treat infections. They work by changing the DNA inside cancer cells to keep them from growing and multiplying.
Anthracyclines
Anthracyclines are anti-tumour 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. Enzymes are proteins that start, help, or speed up the rate of chemical reactions in cells. These drugs are widely used for a variety of cancers.
Examples
- Daunorubicin
- Doxorubicin (Adriamycin)
- Doxorubicin liposomal
- Epirubicin
- Idarubicin
- Valrubicin
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 (cumulative dose) are often placed on these drugs.
Anti-tumour antibiotics that aren’t anthracyclines
- Bleomycin
- Dactinomycin
- Mitomycin-C
- Mitoxantrone (also acts as a topoisomerase II inhibitor, see below)
Topoisomerase inhibitors
These drugs are also called plant alkaloids. They interfere with enzymes (proteins that cause chemical reactions in living cells) called topoisomerases, which help separate the strands of DNA, so they can be copied.
Topoisomerase inhibitors are used to treat certain leukaemias, as well as lung, ovarian, gastrointestinal, colorectal, and pancreatic cancers.
They are grouped according to which type of enzyme they affect:
TOPOISOMERASE I INHIBITORS (CAMPTOTHECINS)
- Irinotecan
- Irinotecan liposomal
- Topotecan
TOPOISOMERASE II INHIBITORS(EPIPODOPHYLLOTOXINS)
- Etoposide (VP-16)
- Mitoxantrone (also acts as an anti-tumour antibiotic)
- Teniposide
These can increase the risk of a second cancer.
Mitotic inhibitors
Mitotic inhibitors are also called plant alkaloids. They are compounds derived from natural products, such as plants. 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.
• Taxanes
- Cabazitaxel
- Docetaxel
- Nab-paclitaxel
- Paclitaxel
• Vinca alkaloids
- Vinblastine
- Vincristine
- Vincristine liposomal
- Vinorelbine
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.
Corticosteroids
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. >> page 10
Examples
- Prednisone
- Methylprednisolone
- Dexamethasone
Steroids are also commonly used to help prevent nausea and vomiting caused by chemotherapy. They are used before some types of chemotherapy to help prevent severe allergic reactions too.
Other chemotherapy drugs
Some chemotherapy drugs act in slightly different ways and don’t fit well into any of the other categories. Here are some examples:
- All-trans-retinoic acid
- Arsenic trioxide
- Asparaginase
- Eribulin
- Hydroxyurea
- Ixabepilone
- Mitotane
- Omacetaxine
- Pegaspargase
- Procarbazine
- Romidepsin
- Vorinostat
Other types of drugs used to treat cancer
Other drugs and biological treatments are used to treat cancer but aren’t considered chemotherapy. They often have different side effects than chemotherapy. Many are used along with surgery, chemotherapy, or radiation therapy.
Targeted therapies
Targeted therapies work by finding specific substances called proteins or receptors that some cancer cells have. The protein or receptor is precisely targeted by the drug, so normal cells aren’t affected by the drugs. This is different than how traditional chemotherapy drugs work. Targeted drugs can be used as the main treatment for a cancer, or they may be used after treatment to keep the cancer under control or keep it from coming back.
Hormone therapy
Drugs in this category work on different actions of hormones that make some cancers grow. These drugs are used to slow the growth of certain breast, prostate, and endometrial (uterine) cancers which normally grow in response to natural sex hormones in the body. They work by making the cancer cells unable to use the hormone they need to grow, or by preventing the body from making the hormone.
Immunotherapy
Immunotherapy is a type of treatment that uses drugs to boost or alter a person’s immune system. These drugs are used with certain types of cancer to help a patient’s immune system recognise and attack cancer cells.
MEET THE EXPERT – Prof Carol-Ann Benn
Prof Carol-Ann Benn heads up an internationally-accredited, multi-disciplinary breast cancer centre at Netcare Milpark Hospital. She lectures at Wits University and, in 2002, established The Breast Health Foundation.
Header image by Adocbe Stock