What is chemotherapy and how does it work to kill cancer?
A Chemical Killer
Chemotherapy is a type of cancer therapy that uses chemicals to attack and destroy cancer cells. These agents are cytotoxic, meaning "toxic to cells.”
Chemotherapy works by attacking rapidly dividing cells in the body, usually through DNA damage or by interrupting the process of cellular division. Since oral and infused chemotherapy treatments are systemic, meaning they travel throughout the body indiscriminately, “healthy” fast-dividing cells throughout the body can be compromised in the process. Some of these rapidly dividing cell types are skin cells, hair cells, cells lining the digestive tract, and blood cells in bone marrow. Cells that are slower to divide and are impacted less frequently, including cartilage, muscle, fat, and nerve cells. Common chemotherapy side effects like nausea, vomiting, hair loss, skin toxicities, diarrhea, and bone weakening can be contributed to how these drugs work in the body.
How does chemotherapy work?
Relevant Terminology
- First-Line Treatment (1L): treatment recommended as the first step for a specific disease or condition; in cancer, the 1st line (1L) treatment is the first line of defense against your cancer and statistically the most likely option to be effective and/or tolerable (less toxic). The 2nd (2L) and 3rd-line (3L) options are those that have shown to be the next best choices if the previous line was ineffective, not effective enough, or had to be discontinued due to allergy or side effect toxicities.
- Adjuvant: treatment given after an initial treatment has completed its course to try to prevent recurrence; for example: if you have surgery followed by chemotherapy, the chemo would be referred to as adjuvant; sometimes adjuvant chemo is casually referred to as "clean-up chemo"
- Chemoembolization: combo therapy that block tumor blood supply and delivers chemo directly to tumor
- Chemoresistant: a cancer that is resistant to or unaffected by chemotherapy
- Chemosensitive: a cancer that is vulnerable/susceptible to chemotherapy
- Complete Response (CR): the disappearance of cancer as the result of a treatment; a complete radiologic response (no cancer seen on a scan) is not the same as a complete pathologic response (no cancer detected in tissue specimens following treatment)
- Conversion Therapy: a treatment intended to make inoperable patients eligible for surgery
- Curative Treatment: treatment that has the intention of completely killing and removing cancer from your body; intended to cure your cancer
- Efficacy: the term used to describe how effective (successful, beneficial, useful, powerful) a treatment is; how well the treatment works. The higher the efficacy, the better it works.
- Growth Factor: a substance in the body (most often a hormone/protein) that influences cellular growth and proliferation; VEGF (vascular endothelial growth factor) is an example of a notable growth factor in cancer. VEGF stimulates the growth of new capillaries to increase blood supply to tissues, including malignant tumors. VEGF inhibitors are a class of targeted therapy in cancer, and they stop/slow the growth of new blood vessel formation to cut off a tumor's access to nourishment.
- Inpatient: a patient who is admitted to the hospital, often for an overnight stay or a procedure that requires a patient to stay overnight in the hospital
- IV Infusion: the delivery of a substance intravenously, or through a vein
- Late-Term Side Effects: side effects that usually don't appear until treatment has ended and can linger for weeks, months, years, or indefinitely after treatment ends
- Long-Term Side Effects: side effects that can begin at any point once treatment has started and can linger for weeks, months, years, or indefinitely after treatment ends
- Lymph Node: small filtering structures packed with immune cells that are found throughout the body, part of the lymphatic system; lymph nodes filter lymph (the fluid that travels through the lymphatic system) in an attempt to remove waste, infections, and other foreign substances from circulation. Lymph nodes can "collect" circulating cancer cells, and the presence of cancer in lymph nodes can indicate that the cancer is spreading beyond the site of origin.
- Lymphedema: swelling (edema) caused by the buildup of lymph fluid in the body
- Mechanism of Action (MOA): the way something functions or operates; describes how drugs and other molecules/compounds interact with the body and achieve an effect on a cellular level
- Micrometastasis: refers to a very small or microscopic cluster of tumor cells somewhere in the body not near the primary tumor, usually less than 1 cm in size and undetectable (or not easily seen) on scans
- NED: No evidence of disease, scans and labs cannot identify any cancer in your body
- Neo-Adjuvant: treatment given before surgery (or before the primary treatment) to reduce the size of tumors and overall tumor burden
- Oral Administration: the delivery of a substance by mouth (pill, capsule, tablet, liquid, etc.)
- Outpatient: a patient who receives services or care from a facility and returns home the same day or a procedure that takes place in a medical
- Palliative Treatment: treatment that has the intention of controlling the cancer so it doesn't grow larger or spread further; not intended to cure your cancer
- Partial Response (PR): the reduction of tumor size or overall tumor burden by a minimum of 25% (usually) as the result of a treatment; reduction by less than 25% is sometimes categorized as "no response" or a "clinically insignificant response."
- Pathology: gross and microscopic study of bodily fluids, cells, tissue, and organs that have been removed from the body
- PICC Line: Peripherally inserted central catheter; a catheter implanted in the upper arm (usually) for easy access to the bloodstream for infusions and blood draws
- Port: Port-a-cath; a catheter implanted surgically in the chest that allows easy access to the bloodstream for infusions and blood draws
- Progression: in cancer, this refers to the cancer's progress (not yours); if there is "progression" it means that the cancer is growing and/or spreading
- Resistant/Refractory: in cancer, this refers to the cancer's reduced vulnerability or lack of susceptibility to treatment; with repeated exposure to a treatment, cancer can develop resistance by using workarounds to avoid the harm intended by the treatment; resistant or refractory cancer is generally more challenging to treat
- ROS (reactive oxygen species): another term for free radicals; unstable molecules that include oxygen and an unpaired electron that can cause damage to important molecules in the body like proteins or DNA; free radicals/ROS are neutralized by antioxidants
- Short-Term Side Effects: side effects that can begin at any point once treatment has started and usually resolve within a brief period of time after treatment ends
- Stable Disease: cancer that is not getting larger or spreading OR getting smaller/disappearing, but rather remaining "as is"
- Standard of Care (SOC): a term used to describe evidence-based diagnostic & treatment guidelines that are applied broadly to patient care in the US, also called Best Standard Care (BSC)
- Systemic Treatment: a treatment that travels through the blood or digestive system, potentially impacting all areas of the body since more of the body is exposed to the treatment
- Tolerability: a characterization of how easy or challenging it is for patients to endure, handle, or make it through the course of treatment; greater tolerability usually aligns with a treatment that causes fewer or less intense side effects
- Toxicity: a characterization of how harmful, severe, disruptive, and tolerable a treatment's side effects are
- Tumor Board: multidisciplinary group of medical professionals who collaborate & review individual patient cases to determine the best courses of treatment, usually includes medical oncologists, radiation oncologists, surgeons, pathologists, and nurses, among others
- Tumor Marker: a type of biomarker that points to and measures the presence of certain types of cancer in the body
Behind the Curtain: Cancer Biology Tidbit
Let's Get a Little Nerdy
Two of the Hallmarks of Cancer, as Hanahan & Weinberg noted in their 2011 paper, are sustained proliferative signaling and evasion of growth suppressors. Chemotherapy agents are designed to go after these specific characteristics of cancer cells, but let's break down what that means before we go any further.
In the body, we have lots of naturally occurring substances that provide direction to cells so they know what to do, when to do it, how long to do it, etc. The body is equipped with numerous genes, for example, whose sole or primary responsibility is to keep cell replication in check and not allow out-of-control cell growth. These genes, the ones that hit the brakes, are called tumor suppressor genes (TSG). TP53, CHEK2, and PTEN are a few examples of tumor suppressor genes that we all have in our bodies, and these three are often mutated (changed; not working properly) in cancer. When these protective genes don't work properly, cancer cells are given a thumbs up to grow, divide, replicate, and prosper. This is a problem.
Furthermore, cancer cells (b*stards that they are) can tap into another mechanism to enable unrestricted growth—they can create more growth factors. What's a growth factor? Growth factors are proteins that regulate and encourage cellular growth, though they may also have additional responsibilities in the body. Insulin is an example of a growth factor. When growth factors attach to and activate receptors on a cell’s surface (like the blue ones in the photo to the left), they trigger signaling within the cell that can initiate replication. For our purposes, we can think of growth factors like gas pedals for cellular growth. In cancer, these growth factors may be overproduced and overwhelm cells with continuous growth signals. This is like placing a brick on the gas pedal. Now, we have an even bigger problem.
This is when chemotherapy can step in and try to course correct. The cancer has manipulated cells to continue growing and dividing, and the chemotherapy is going to hit the bloodstream, laser-focused on locating and destroying any and all fast-dividing cells.
Chemotherapy Response Rates by cancer type (2020)
