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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

Structure of 5FU with the fluor group in carbon 5-position. 5FU is a pyrimidine analog drug whose mechanism of action is through irreversible inhibition of thymidylate synthase (TS). Clinically is have been used in the treatment of anal, breast, colorectal, esophageal, stomach, pancreatic and skin cancers.
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Figure 1: Structure of 5FU with the fluor group in carbon 5-position. 5FU is a pyrimidine analog drug whose mechanism of action is through irreversible inhibition of thymidylate synthase (TS). Clinically is have been used in the treatment of anal, breast, colorectal, esophageal, stomach, pancreatic and skin cancers.

Mentions: The pyrimidine 5-fluorouracil (5FU) has been under investigation for the treatment of human cancers since 1954 when it was observed that uracil is utilized more efficiently by tumor cells than normal cells [11]. The knowledge that fluorine substitutions of hydrogen in metabolites often resulted in a toxic compound inspired the design of 5FU (Figure 1) and testing as a tumor-inhibiting compound [11–13]. Since its discovery, 5FU has been used as a treatment for many solid tumors such as colon, breast, head and neck cancers, and advanced pancreatic cancer. For 20 years, 5FU was regarded as the only effective drug against advanced pancreatic cancer. However, despite numerous efforts to improve therapy outcomes, the best response rate was approximately 20% [12,14,15].


Antimetabolite Treatment for Pancreatic Cancer.

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

Structure of 5FU with the fluor group in carbon 5-position. 5FU is a pyrimidine analog drug whose mechanism of action is through irreversible inhibition of thymidylate synthase (TS). Clinically is have been used in the treatment of anal, breast, colorectal, esophageal, stomach, pancreatic and skin cancers.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Structure of 5FU with the fluor group in carbon 5-position. 5FU is a pyrimidine analog drug whose mechanism of action is through irreversible inhibition of thymidylate synthase (TS). Clinically is have been used in the treatment of anal, breast, colorectal, esophageal, stomach, pancreatic and skin cancers.
Mentions: The pyrimidine 5-fluorouracil (5FU) has been under investigation for the treatment of human cancers since 1954 when it was observed that uracil is utilized more efficiently by tumor cells than normal cells [11]. The knowledge that fluorine substitutions of hydrogen in metabolites often resulted in a toxic compound inspired the design of 5FU (Figure 1) and testing as a tumor-inhibiting compound [11–13]. Since its discovery, 5FU has been used as a treatment for many solid tumors such as colon, breast, head and neck cancers, and advanced pancreatic cancer. For 20 years, 5FU was regarded as the only effective drug against advanced pancreatic cancer. However, despite numerous efforts to improve therapy outcomes, the best response rate was approximately 20% [12,14,15].

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