Chemotherapy mechanism of action
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Chemotherapy Mechanism of Action: DNA Damage, Cell Death, and Immune Modulation
DNA Targeting and Inhibition of Cell Growth
Many chemotherapy drugs, such as cisplatin and other platinum-based agents, work by entering cancer cells and binding to DNA. This binding forms DNA adducts, which block DNA synthesis and cell division, ultimately leading to cell death. If the DNA damage is not repaired, the cell cannot survive or replicate, resulting in the inhibition of tumor growth 145.
Induction of Apoptosis and Cell Death Pathways
Chemotherapy drugs can trigger programmed cell death (apoptosis) through several mechanisms. These include the activation of p53 signaling, cell cycle arrest, and the upregulation of pro-apoptotic genes. In some cases, chemotherapy can also induce necrosis, another form of cell death, depending on the drug dose and the metabolic state of the cancer cell. Both apoptosis and necrosis can occur together within a tumor, contributing to the overall effectiveness of chemotherapy 14.
Effects on Cellular Proteins and Other Biomolecules
In addition to DNA, chemotherapy agents like cisplatin can bind to other cellular components such as RNA and proteins. These interactions can disrupt various cellular processes and contribute to the cytotoxic effects of the drugs. The binding to non-DNA targets is also linked to the development of drug resistance and side effects 45.
Modulation of the Tumor Microenvironment and Immune System
Chemotherapy does not only act directly on cancer cells. It also affects the tumor microenvironment and the immune system. Some chemotherapeutic agents can make dying tumor cells more visible to immune cells, stimulate both innate and adaptive immune responses, and even reverse tumor-induced immunosuppression. These immune-based effects can enhance the overall antitumor response and are important for the success of chemotherapy 237.
Inflammatory Responses and Signaling Pathways
Chemotherapy drugs can trigger inflammation in the tumor microenvironment by activating signaling pathways such as NF-kB and MAPK. While inflammation can help suppress tumor growth, it can also create conditions that promote cancer progression and relapse. Managing this double-edged effect is important for improving treatment outcomes .
Drug Resistance Mechanisms
A major challenge in chemotherapy is the development of multidrug resistance (MDR). Cancer cells can become resistant through several mechanisms, including increased drug efflux by ABC transporters (like ABCB1), enhanced DNA repair, and genetic changes. Overcoming MDR is a key focus in current cancer research, with strategies such as combining chemotherapy with inhibitors of drug efflux pumps or using natural compounds to sensitize cancer cells 568910.
Conclusion
Chemotherapy works through multiple mechanisms: damaging DNA, disrupting cellular processes, inducing cell death, modulating the immune system, and affecting the tumor microenvironment. However, its effectiveness can be limited by drug resistance and side effects. Understanding these mechanisms is crucial for developing better cancer treatments and combination therapies that can overcome resistance and improve patient outcomes 12345678+2 MORE.
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