How do cytostatic agents work?
Author: Gesche Tallen, MD, PhD, Editor: Maria Yiallouros, Reviewer: Prof. Dr. med. Dr. h.c. Günter Henze, English Translation: Hannah McRae, Last modification: 2015/04/27
The anticancer effect of a cytostatic drug is provided by its mechanism of action. Different cytostatics show different properties and modes of action, which is mainly due to the structure of the herbal and/or the chemical substance from which the drug has been derived. Based on how a cytostatic works, it forms part of a so-called substance group, each of which comprises the cytostatic agents that show similar characteristics (like chemical properties / modes of action).
To understand how cytostatics work, it is important to know about the life cycle of a cell, regardless of whether it is healthy or sick, benign or malignant.
The life of a cell is determined by the so-called cell cycle. Many different signalling pathways, which involve numerous proteins with various tasks, control – like an inner clock – the phases of the cell cycle. They determine when and how often the cell divides, when it matures, when it “sleeps,” when it “wakes up” and divides again, when it ages, and when it dies.
Cancer cells have lost their inner clock. As a result, they multiply rapidly, do not mature properly, and often become immortal.
Chemotherapy and radiation (and many other external factors) can cause stress in proliferating cells. As a consequence, their growth-regulating mechanisms get damaged. If a cell cannot repair this damage, it stops growing or dies.
Most molecular components of the different cytostatic groups can only affect those phases of the cell cycle that involve cell division. This mechanism particularly refers to the so-called cell-cycle-specific cytotoxic drugs. There are a few cytostatic agents that can affect a cell in any phase of the cell cycle. These are the so-called phase-nonspecific cytotoxic drugs.
The majority of cytostatic drugs adversely affect healthy cells in various ways. They particularly target those dividing frequently. These include bone marrow (i.e. blood stem cells), oral and gastrointestinal mucosa as well as hair follicle cells. Fast-growing tissues are therefore very sensitive to cytostatic drugs. Hence, malignant tumours are generally more susceptible to chemotherapy than benign ones, since the latter usually grow slowly.
Even in rapidly growing tissues, there are temporarily inactive, dormant cells that do not participate in cell division (mitosis) for a while. But they can start proliferating again at any time. In order to not miss these moments and successfully treat these kinds of cancer cells as well, phase-specific and phase-nonspecific cytostatic drugs are usually combined (polychemotherapy).
Depending on their specific mechanism of action, cytostatic drugs interfere with mitosis in different ways, for example by damaging the genetic material (DNA) of a cell. If the cancer cell dies after treatment with a cytostatic drug (processes called apoptosis, which means programmed cell death, or necrosis) or turns into a less immature cell (a process called differentiation), chemotherapy has succeeded. If the cancer cells can repair the damage caused by the “cytostatic stress,” they become resistant and therefore do not respond to the treatment.