Limits...
Antimetabolite Treatment for Pancreatic Cancer.

Valenzuela MM, Neidigh JW, Wall NR - Chemotherapy (Los Angel) (2014)

Bottom Line: Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4-8 months.Unfortunately, efforts to improve chemotherapy regimens by combining, 5-fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improved patient survival.However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient's overall survival.

View Article: PubMed Central - PubMed

Affiliation: Center for Health Disparities Research and Molecular Medicine, Loma Linda University, Loma Linda, California, USA ; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, California, USA.

ABSTRACT

Pancreatic cancer is a deadly and aggressive disease. Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4-8 months. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine and 5-fluorouracil are used clinically. Unfortunately, efforts to improve chemotherapy regimens by combining, 5-fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improved patient survival. The novel antimetabolite zebularine shows promise, inducing apoptosis and arresting cellular growth in various pancreatic cancer cell lines. However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient's overall survival.

No MeSH data available.


Related in: MedlinePlus

Zebularine’s structure includes a 2(1H)-pyrimidinone ring. It is a nucleoside analog of cytidine and works by inhibiting cytidine deaminase by binding to the active site as a covalent hydrates. It has also been shown to inhibit DNA methylation and tumor growth in vivo and in vitro. Though entirely experimental at this time, it has been suggested that it could be used as a chemoprevention agent or even in epigenetic therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494102&req=5

Figure 7: Zebularine’s structure includes a 2(1H)-pyrimidinone ring. It is a nucleoside analog of cytidine and works by inhibiting cytidine deaminase by binding to the active site as a covalent hydrates. It has also been shown to inhibit DNA methylation and tumor growth in vivo and in vitro. Though entirely experimental at this time, it has been suggested that it could be used as a chemoprevention agent or even in epigenetic therapy.

Mentions: Epigenetic changes accompany pancreatic tumorigenesis as well as the acquisition of resistance to chemotherapy [53,54]. Therapeutic agents that alter the epigenetic state of pancreatic cancer cells are under investigation as cytotoxic agents as well as agents to reverse acquired resistance to first-line agents. Lacking an amino group on the C-4 position of the pyrimidine ring, zebularine ((1-β-D-Ribofuranosyl)-2(1H)-pyrimidinone), a cytidine analogue (Figure 7), was originally developed as a cytidine deaminase inhibitor. It is also a novel DNA methytransferase (DNMT) inhibitor and unlike other DNMT inhibitors, zebularine is more stable in aqueous solution and is less toxic in vitro and in vivo [55–57]. Continuous exposure of numerous cancer cell lines to zebularine slowed tumor cell growth as compared to normal human fibroblast cell lines indicating its promise as a chemotherapy agent for cancer treatment [58].


Antimetabolite Treatment for Pancreatic Cancer.

Valenzuela MM, Neidigh JW, Wall NR - Chemotherapy (Los Angel) (2014)

Zebularine’s structure includes a 2(1H)-pyrimidinone ring. It is a nucleoside analog of cytidine and works by inhibiting cytidine deaminase by binding to the active site as a covalent hydrates. It has also been shown to inhibit DNA methylation and tumor growth in vivo and in vitro. Though entirely experimental at this time, it has been suggested that it could be used as a chemoprevention agent or even in epigenetic therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494102&req=5

Figure 7: Zebularine’s structure includes a 2(1H)-pyrimidinone ring. It is a nucleoside analog of cytidine and works by inhibiting cytidine deaminase by binding to the active site as a covalent hydrates. It has also been shown to inhibit DNA methylation and tumor growth in vivo and in vitro. Though entirely experimental at this time, it has been suggested that it could be used as a chemoprevention agent or even in epigenetic therapy.
Mentions: Epigenetic changes accompany pancreatic tumorigenesis as well as the acquisition of resistance to chemotherapy [53,54]. Therapeutic agents that alter the epigenetic state of pancreatic cancer cells are under investigation as cytotoxic agents as well as agents to reverse acquired resistance to first-line agents. Lacking an amino group on the C-4 position of the pyrimidine ring, zebularine ((1-β-D-Ribofuranosyl)-2(1H)-pyrimidinone), a cytidine analogue (Figure 7), was originally developed as a cytidine deaminase inhibitor. It is also a novel DNA methytransferase (DNMT) inhibitor and unlike other DNMT inhibitors, zebularine is more stable in aqueous solution and is less toxic in vitro and in vivo [55–57]. Continuous exposure of numerous cancer cell lines to zebularine slowed tumor cell growth as compared to normal human fibroblast cell lines indicating its promise as a chemotherapy agent for cancer treatment [58].

Bottom Line: Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4-8 months.Unfortunately, efforts to improve chemotherapy regimens by combining, 5-fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improved patient survival.However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient's overall survival.

View Article: PubMed Central - PubMed

Affiliation: Center for Health Disparities Research and Molecular Medicine, Loma Linda University, Loma Linda, California, USA ; Department of Basic Sciences, Division of Biochemistry, Loma Linda University, Loma Linda, California, USA.

ABSTRACT

Pancreatic cancer is a deadly and aggressive disease. Less than 1% of diagnosed patients survive 5 years with an average survival time of only 4-8 months. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine and 5-fluorouracil are used clinically. Unfortunately, efforts to improve chemotherapy regimens by combining, 5-fluorouracil or gemcitabine with other drugs, such as cisplatin or oxaliplatin, have not increased cell killing or improved patient survival. The novel antimetabolite zebularine shows promise, inducing apoptosis and arresting cellular growth in various pancreatic cancer cell lines. However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient's overall survival.

No MeSH data available.


Related in: MedlinePlus