Chemotherapy: How it Works and Side Effects

How does chemotherapy target cancer cells? 

By targeting rapidly dividing cells

Chemotherapy targets cancer cells primarily by exploiting their characteristic of rapid and uncontrolled division. Here’s a breakdown of how it works:

• Interfering with Cell Division: Chemotherapy drugs are designed to disrupt the process of cell division (mitosis). They can do this in several ways:
  • Damaging DNA: Some drugs directly damage the DNA of the cancer cells, making it impossible for them to replicate properly and divide.
  • Interfering with DNA Synthesis: Other drugs act as antimetabolites, mimicking the building blocks of DNA and RNA. When cancer cells incorporate these faulty building blocks, it halts DNA replication and prevents cell division.
  • Inhibiting Protein Synthesis: Certain chemotherapy agents interfere with the production of proteins that are essential for cell growth and division.
  • Disrupting Mitotic Spindles: Some drugs, like vinca alkaloids and taxanes, interfere with the formation of microtubules, which are crucial structures for separating chromosomes during cell division. This leads to cell cycle arrest and cell death.
  • Inhibiting Topoisomerases: These enzymes are necessary for DNA replication and repair. Some chemotherapy drugs block their action, causing DNA damage and preventing cell division.
• Selectivity Based on Rapid Division: Cancer cells typically divide much more frequently than most normal cells in the body. Chemotherapy drugs are more effective against rapidly dividing cells, which is why they preferentially target cancer cells.
• Systemic Treatment: Most chemotherapy drugs are administered intravenously or orally, allowing them to circulate throughout the bloodstream and reach cancer cells throughout the body. This is particularly important for cancers that have spread (metastasized).

Is chemotherapy selective for cancer cells? 

No, it affects all rapidly dividing cells, including healthy ones  

chemotherapy is designed to target rapidly dividing cells, it is not perfectly selective for cancer cells.   

As you mentioned, chemotherapy affects all rapidly dividing cells in the body, including healthy ones. This lack of precise targeting is the reason behind many of the common and often unpleasant side effects associated with chemotherapy.   

Healthy cells that frequently divide and are therefore susceptible to damage from chemotherapy include:

• Hair follicle cells: Leading to hair loss (alopecia).
• Cells lining the digestive system: Causing nausea, vomiting, diarrhea, and mouth sores (mucositis).   
• Bone marrow cells: Resulting in a decrease in blood cell production, which can lead to:
  • Neutropenia: Increased risk of infection due to low white blood cell count.   
  • Anemia: Fatigue and weakness due to low red blood cell count.   
  • Thrombocytopenia: Increased risk of bleeding and bruising due to low platelet count.   

What are the different routes of chemotherapy administration?

Intravenous (IV), oral, intramuscular (IM),  subcutaneous (SC), topical, intra-arterial, intraperitoneal, etc.   

Chemotherapy drugs can be administered through various routes to reach cancer cells in different parts of the body. Here’s a more detailed explanation of the routes you listed and a few others:  

Systemic Routes (affecting the whole body):

• Intravenous (IV): This is the most common route. The chemotherapy drug is delivered directly into a vein through a needle or a catheter. This allows the drug to circulate throughout the bloodstream. Different types of IV access devices include:
  • Peripheral IV line: A temporary catheter inserted into a vein in the arm or hand.  
  • Central venous catheter (CVC): A longer-term catheter inserted into a large vein in the chest or arm. Types include tunneled catheters (e.g., Hickman, Broviac), peripherally inserted central catheters (PICCs), and implantable ports (port-a-cath).  

• Oral: Some chemotherapy drugs are available as pills, capsules, or liquids that are swallowed. This is a convenient route for some patients and cancers.  
• Intramuscular (IM): The drug is injected directly into a muscle, usually in the upper arm, thigh, or buttocks. Absorption into the bloodstream is slower than with IV administration.  
• Subcutaneous (SC): The drug is injected into the layer of tissue just beneath the skin. This route is typically used for smaller volumes of medication that can be absorbed relatively easily.

Regional Routes (targeting a specific area):

• Topical: Chemotherapy creams or gels are applied directly to the skin to treat certain types of skin cancer. This limits the drug’s effect primarily to the treated area.  
• Intra-arterial: The chemotherapy drug is injected directly into an artery that supplies blood to the tumor. This delivers a high concentration of the drug directly to the cancer while limiting exposure to other parts of the body.  
• Intraperitoneal (IP): The drug is delivered directly into the abdominal cavity. This is often used to treat cancers that have spread within the abdomen, such as ovarian cancer. Sometimes, this is done with heated chemotherapy (Hyperthermic Intraperitoneal Chemotherapy – HIPEC) during surgery.  
• Intrathecal: The chemotherapy drug is injected directly into the cerebrospinal fluid (CSF), the fluid surrounding the brain and spinal cord. This is used to treat cancers that have spread to the central nervous system, such as some types of leukemia and lymphoma. This is typically done via a lumbar puncture (spinal tap) or through an Ommaya reservoir, a device implanted under the scalp.  
• Intrapleural: The chemotherapy drug is administered into the pleural space, the area between the two layers of tissue that surround the lungs. This can be used to treat cancers affecting the pleura, such as malignant pleural mesothelioma or lung cancer that has spread to the pleura, and to manage malignant pleural effusions (fluid buildup).
• Intravesical: The chemotherapy drug is instilled directly into the bladder through a catheter. This is used to treat non-muscle-invasive bladder cancer, targeting cancer cells on the bladder’s inner lining.  
• Intralesional: The drug is injected directly into a tumor. This is feasible when the tumor is accessible and can be safely reached with a needle.  

The choice of administration route depends on several factors, including:

• The type and location of the cancer
• The specific chemotherapy drugs being used
• The patient’s overall health  
• The goals of treatment (e.g., cure, control, palliation)

What are the different treatment intents or goals of chemotherapy? 

Curative, adjuvant, neoadjuvant, palliative

Chemotherapy can be used with different intentions or goals depending on the specific cancer, its stage, and the patient’s overall health. Here’s a breakdown of the treatment intents you mentioned:

• Curative Chemotherapy: The primary goal here is to eradicate the cancer completely so that it doesn’t come back. This approach is typically used when the cancer is localized or hasn’t spread extensively. The aim is to achieve a long-term, disease-free survival. Examples include chemotherapy for some types of lymphoma, leukemia, and testicular cancer.
• Adjuvant Chemotherapy: This type of chemotherapy is given after the primary treatment, such as surgery or radiation therapy, to eliminate any remaining microscopic cancer cells that may not be visible or detectable. The goal is to prevent recurrence (the cancer coming back). It acts as an “insurance policy” to mop up any stray cancer cells that might have spread but haven’t formed new tumors yet. Adjuvant chemotherapy is commonly used in breast cancer, colon cancer, and lung cancer, among others.
• Neoadjuvant Chemotherapy: This chemotherapy is given before the primary treatment, such as surgery or radiation therapy. The main goals of neoadjuvant chemotherapy are to:
  • Shrink the tumor: This can make surgery easier and more effective, potentially allowing for less extensive surgery.
  • Destroy micrometastases: It can address any small areas of cancer spread that may exist but are not yet visible.
  • Assess the tumor’s response to chemotherapy: This can help doctors determine if the chosen drugs are effective for that particular cancer. Examples include neoadjuvant chemotherapy for breast cancer, esophageal cancer, and bladder cancer.
• Palliative Chemotherapy: When a cancer is advanced, has spread widely (metastasized), and a cure is unlikely, the goal of palliative chemotherapy shifts to managing the disease and improving the patient’s quality of life. The aims include:
  • Slowing down the growth and spread of the cancer.
  • Relieving symptoms such as pain, pressure, or obstruction caused by the tumor.
  • Prolonging survival for as long as possible. Palliative chemotherapy focuses on controlling the cancer and alleviating its effects rather than eliminating it.

Are there different classes of chemotherapy drugs, and how do they work differently? 

Yes, alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, etc., each targeting different parts of cell division.

There are several classes of chemotherapy drugs, and they work by targeting different essential processes within cancer cells, often focusing on disrupting cell division at various stages. Here’s a breakdown of the classes you mentioned and how they generally work:  

• Alkylating Agents:
  • How they work: These drugs directly damage the DNA of cancer cells. They add an alkyl group (a type of chemical structure) to the DNA, which interferes with its ability to replicate and function properly. This damage can lead to breaks in the DNA strands and ultimately cell death.  
  • Cell cycle specificity: They are generally considered cell cycle non-specific, meaning they can affect cells in any phase of the cell cycle, including the resting phase. However, they are most effective against rapidly dividing cells.  
  • Examples: Cyclophosphamide, cisplatin, carboplatin, melphalan, temozolomide.
• Antimetabolites:
  • How they work: These drugs are structurally similar to natural substances (metabolites) that cells need for DNA and RNA synthesis. They “trick” cancer cells into taking them up instead of the normal metabolites. Once inside the cell, they interfere with the enzymes involved in DNA and RNA production, ultimately halting cell growth and division.  
  • Cell cycle specificity: They are typically cell cycle specific, often working during the S phase (DNA synthesis phase) of the cell cycle.
  • Examples: Methotrexate, 5-fluorouracil (5-FU), cytarabine, gemcitabine, capecitabine.  
• Topoisomerase Inhibitors:
  • How they work: Topoisomerases are enzymes that help to unwind and rewind DNA during replication and transcription. Topoisomerase inhibitors interfere with these enzymes.
    • Topoisomerase I inhibitors: They create DNA strand breaks and prevent the resealing of these breaks, leading to DNA damage and cell death.  
    • Topoisomerase II inhibitors: They also cause DNA strand breaks and prevent the DNA from being properly untangled, which is necessary for cell division.  

• Cell cycle specificity: They are generally cell cycle specific, often most active during the S and G2 phases (DNA synthesis and pre-mitotic phases).
• Examples:
  • Topoisomerase I inhibitors: Irinotecan, topotecan.  
  • Topoisomerase II inhibitors: Etoposide, teniposide, doxorubicin (also an anthracycline antibiotic with other mechanisms).  
• Mitotic Inhibitors:
  • How they work: These drugs interfere with the process of mitosis (cell division) by disrupting the formation and function of microtubules. Microtubules are protein fibers that are essential for separating chromosomes during cell division. By disrupting microtubules, these drugs prevent cancer cells from dividing into two new cells.
    • Vinca alkaloids: Prevent the formation of microtubules.  
    • Taxanes: Prevent the breakdown of microtubules, essentially freezing the mitotic spindle.  

• Cell cycle specificity: They are cell cycle specific, acting primarily during the M phase (mitosis) of the cell cycle.
• Examples:
  • Vinca alkaloids: Vincristine, vinblastine, vinorelbine.  
  • Taxanes: Paclitaxel, docetaxel, cabazitaxel.