Related Experiment Video
Updated: May 9, 2026
Proximity Ligand Assay to Localize Proteins in DNA Damage Sites
Published on: August 2, 2024
DNA alkylation damage and autophagy induction
Diana L Bordin1, Michelle Lima1, Guido Lenz1
1Departamento de Biofísica/Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP 91501-970 Porto Alegre, RS, Brazil.
Abstract:
Many alkylating agents are used as chemotherapeutic drugs and have a long history of clinical application. These agents inflict a wide range of DNA damage resulting in a complex cellular response. After DNA damage, cells trigger a series of signaling cascades promoting cellular survival and cell cycle blockage which enables time for DNA repair to occur. More recently, induction of autophagy has been observed in cancer cells after treatment with different DNA-targeted anticancer drugs, including alkylating agents. Several studies have demonstrated that induction of autophagy after DNA damage delays apoptotic cell death and may therefore lead to chemoresistance, which is the limiting factor for successful chemotherapy. On the other hand, depending on the extent of damage and the cellular context, the induction of autophagy may also contribute to cell death. Given these conflicting results, many studies have been conducted to better define the role of autophagy in cancer cells in response to chemotherapy. In this review, we describe the main alkylating agents used in clinical oncology as well as the cellular response they evoke with emphasis on autophagy.
Insights
Alkylating agents cause DNA damage, triggering cellular responses including autophagy. This review explores how autophagy impacts chemotherapy effectiveness, potentially causing chemoresistance or cell death.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Alkylating agents are widely used chemotherapy drugs that induce DNA damage.
- Cancer cells exhibit complex responses to DNA damage, including cell cycle arrest and DNA repair.
- Autophagy induction is a recently observed response to DNA-targeting drugs like alkylating agents.
Purpose of the Study:
- To review the primary alkylating agents used in clinical oncology.
- To elucidate the cellular responses elicited by these agents, with a specific focus on autophagy.
- To clarify the dual role of autophagy in cancer cell response to chemotherapy.
Main Methods:
- Literature review of clinical oncology studies.
- Analysis of cellular signaling cascades following DNA damage.
- Examination of research on autophagy induction by alkylating agents.
Main Results:
- Alkylating agents cause diverse DNA damage, initiating signaling pathways for survival and repair.
- Autophagy induction in cancer cells treated with alkylating agents can delay apoptosis.
- The role of autophagy in chemotherapy is context-dependent, potentially leading to chemoresistance or cell death.
Conclusions:
- Autophagy's role in chemotherapy response is complex and debated.
- Understanding autophagy is crucial for overcoming chemoresistance.
- Further research is needed to define autophagy's precise impact on chemotherapy outcomes.
Related Concept Videos
02:36DNA Damage can Stall the Cell Cycle
02:36DNA Damage Can Stall the Cell Cycle
01:18Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
01:08Nucleotide Excision Repair