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Programmed cell death (apoptosis) and response to anti-cancer drugs
1Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam.
Abstract:
Programmed cell death (apoptosis) is a conserved, natural mechanism for the removal of redundant and unwanted cells during normal development. This article reviews the evidence that apoptosis may also control the response of tumor cells to treatment with cytostatic drugs. Whereas most clinically used anti-cancer drugs can activate late events of apoptosis (DNA degradation and morphological changes) there are differences in essential signalling pathways between pharmacological cell death and the physiological induction of an active suicide programme. However, deregulation of normally integrated cell cycle progression appears a central signalling event in most forms of apoptosis, linking cell cycle control, DNA repair and cell death. Whether apoptosis is the cause or the consequence of drug-induced cell death remains to be established.
Insights
Programmed cell death (apoptosis) removes unwanted cells and may control tumor cell response to anti-cancer drugs. Deregulation of cell cycle progression links DNA repair and cell death, but its role in drug-induced cell death needs further study.
Area of Science:
- Cell Biology
- Cancer Research
- Pharmacology
Background:
- Programmed cell death, or apoptosis, is a natural process for eliminating unnecessary cells during development.
- This review examines apoptosis's role in how tumor cells respond to cytostatic drugs.
- Existing anti-cancer drugs can trigger late-stage apoptosis, but signaling pathways differ from natural apoptosis.
Purpose of the Study:
- To review evidence on apoptosis controlling tumor cell response to cytostatic drugs.
- To explore the signaling pathway differences between drug-induced and physiological apoptosis.
- To investigate the link between cell cycle deregulation, DNA repair, and cell death in cancer treatment.
Main Methods:
- Literature review of programmed cell death and cancer drug response.
- Analysis of signaling pathways in physiological and pharmacological apoptosis.
- Examination of cell cycle control, DNA repair, and cell death mechanisms.
Main Results:
- Most anti-cancer drugs activate late apoptotic events like DNA degradation.
- Significant differences exist in signaling pathways between pharmacological and physiological apoptosis.
- Cell cycle deregulation is a central event in apoptosis, connecting cell cycle control, DNA repair, and cell death.
Conclusions:
- Apoptosis plays a role in tumor cell response to cytostatic drugs.
- Understanding the distinct signaling pathways is crucial for cancer therapy.
- The precise causal relationship between apoptosis and drug-induced cell death requires further investigation.