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Published on: November 19, 2019
DNA damage response and repair in pancreatic cancer development and therapy
Parnia Rahnamay Farnood1, Romina Danesh Pazhooh1, Zatollah Asemi2
1Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
Abstract:
Pancreatic cancer (PC) is among fatal malignancies, with a dismal prognosis and a low survival rate of 5-10%. In both sporadic and inherited PC, gene alterations, such as BRCA1/2, PALB2, and ATM, can occur frequently. Currently, surgery, chemo- and radio-therapy are the most common therapeutic strategies for treating this cancer. DNA damage response (DDR) establishes multiple pathways that eliminate DNA damage sites to maintain genomic integrity. Various types of cancers and age-related diseases are associated with DDR machinery defects. According to the severity of the damage, DDR pathways respond appropriately to lesions through repairing damage, arresting the cell cycle, or apoptosis. Recently, novel agents, particularly those targeting DDR pathways, are being utilized to improve the response of many cancers to chemotherapy and radiotherapy. In this paper, we briefly reviewed DDR processes and their components, including DDR sensors, DDR mediators, and DDR transducers in the progression, prognosis, and treatment of PC.
Insights
Pancreatic cancer (PC) has a low survival rate. This review explores DNA damage response (DDR) pathways and their role in PC progression and treatment, highlighting potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic cancer (PC) is a highly fatal malignancy with a 5-10% survival rate.
- Gene alterations like BRCA1/2, PALB2, and ATM are common in PC.
- Current treatments include surgery, chemotherapy, and radiotherapy.
Purpose of the Study:
- To review DNA damage response (DDR) processes and components in pancreatic cancer.
- To elucidate the role of DDR in PC progression, prognosis, and treatment.
- To highlight novel therapeutic strategies targeting DDR pathways.
Main Methods:
- Literature review of DNA damage response (DDR) pathways.
- Analysis of DDR components (sensors, mediators, transducers).
- Examination of DDR's role in pancreatic cancer progression and treatment.
Main Results:
- Defects in DDR machinery are linked to various cancers and age-related diseases.
- DDR pathways repair DNA damage, arrest cell cycle, or induce apoptosis.
- Novel agents targeting DDR pathways show promise in improving cancer treatment response.
Conclusions:
- Understanding DDR pathways is crucial for pancreatic cancer management.
- Targeting DDR offers a promising strategy to enhance chemotherapy and radiotherapy efficacy.
- Further research into DDR components could lead to improved PC prognosis and treatment outcomes.
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