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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

Cisplatin has two chloride ions and two amine groups attached to the center platinum ion. Cisplatin has been used to treat various cancers which include sarcomas carcinomas of the lung and ovary, lymphomas and germ cell tumors and is especially effective in treatment of testicular cancer.
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Figure 5: Cisplatin has two chloride ions and two amine groups attached to the center platinum ion. Cisplatin has been used to treat various cancers which include sarcomas carcinomas of the lung and ovary, lymphomas and germ cell tumors and is especially effective in treatment of testicular cancer.

Mentions: Platinum agents are used today in combination therapy regimes with gemcitabine as second line chemotherapy for metastatic pancreatic cancer. Cisplatin (dis-diamminedichloroplatinum, CDDP, PtCl2(NH3)2) is shown in Figure 5 and is an inorganic platinum complex composed of a doubly charged platinum ion, and four ligands-two chloride ions and two amines. Cisplatin is a potent chemotherapy drug discovered in the 1960’s. It is widely used today against a variety of tumors including head and neck, non-small cell lung, stomach and bladder cancers, non-Hodgkin’s lymphoma and sarcomas [39,40], Oxaliplatin (trans-l-1,2-diaminocyclohexane oxalatoplatinum) (Figure 6) is a new platinum agent that is more potent in vitro and has a better toxicity profile compared to cisplatin, as it only needs a small number of DNA adducts to attain the same cytotoxicity profile as cisplatin. In preclinical studies, oxaliplatin shows efficacy in a number of cancer cell lines, which also includes cell lines that are cisplatin resistant [41,42]. This provides hope that with minor modification of these platinum compounds, not only will efficacy increase, but resistance will decrease as well.


Antimetabolite Treatment for Pancreatic Cancer.

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

Cisplatin has two chloride ions and two amine groups attached to the center platinum ion. Cisplatin has been used to treat various cancers which include sarcomas carcinomas of the lung and ovary, lymphomas and germ cell tumors and is especially effective in treatment of testicular cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Cisplatin has two chloride ions and two amine groups attached to the center platinum ion. Cisplatin has been used to treat various cancers which include sarcomas carcinomas of the lung and ovary, lymphomas and germ cell tumors and is especially effective in treatment of testicular cancer.
Mentions: Platinum agents are used today in combination therapy regimes with gemcitabine as second line chemotherapy for metastatic pancreatic cancer. Cisplatin (dis-diamminedichloroplatinum, CDDP, PtCl2(NH3)2) is shown in Figure 5 and is an inorganic platinum complex composed of a doubly charged platinum ion, and four ligands-two chloride ions and two amines. Cisplatin is a potent chemotherapy drug discovered in the 1960’s. It is widely used today against a variety of tumors including head and neck, non-small cell lung, stomach and bladder cancers, non-Hodgkin’s lymphoma and sarcomas [39,40], Oxaliplatin (trans-l-1,2-diaminocyclohexane oxalatoplatinum) (Figure 6) is a new platinum agent that is more potent in vitro and has a better toxicity profile compared to cisplatin, as it only needs a small number of DNA adducts to attain the same cytotoxicity profile as cisplatin. In preclinical studies, oxaliplatin shows efficacy in a number of cancer cell lines, which also includes cell lines that are cisplatin resistant [41,42]. This provides hope that with minor modification of these platinum compounds, not only will efficacy increase, but resistance will decrease as well.

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