Challenges of drug resistance in the management of pancreatic cancer.

Hdl Handle:
http://hdl.handle.net/10147/207899
Title:
Challenges of drug resistance in the management of pancreatic cancer.
Authors:
Sheikh, Rizwan; Walsh, Naomi; Clynes, Martin; O'Connor, Robert; McDermott, Ray
Affiliation:
Adelaide and Meath Hospital incorporating The National Children's Hospital,, Tallaght, Dublin 24, Ireland. sheikh.rizwan68@gmail.com
Citation:
Expert Rev Anticancer Ther. 2010 Oct;10(10):1647-61.
Journal:
Expert review of anticancer therapy
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207899
DOI:
10.1586/era.10.148
PubMed ID:
20942635
Abstract:
The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.
Language:
eng
MeSH:
Antineoplastic Agents/*therapeutic use; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Deoxycytidine/*analogs & derivatives/therapeutic use; *Drug Resistance, Neoplasm; Fluorouracil/*analogs & derivatives/therapeutic use; Humans; Neoplasm Metastasis; Pancreatic Neoplasms/*drug therapy/genetics/pathology/radiotherapy; Protein Kinase Inhibitors/therapeutic use; Quinazolines/*therapeutic use; Receptor, Epidermal Growth Factor/antagonists & inhibitors; Treatment Outcome; Tumor Microenvironment
ISSN:
1744-8328 (Electronic); 1473-7140 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorSheikh, Rizwanen_GB
dc.contributor.authorWalsh, Naomien_GB
dc.contributor.authorClynes, Martinen_GB
dc.contributor.authorO'Connor, Roberten_GB
dc.contributor.authorMcDermott, Rayen_GB
dc.date.accessioned2012-02-01T10:49:31Z-
dc.date.available2012-02-01T10:49:31Z-
dc.date.issued2012-02-01T10:49:31Z-
dc.identifier.citationExpert Rev Anticancer Ther. 2010 Oct;10(10):1647-61.en_GB
dc.identifier.issn1744-8328 (Electronic)en_GB
dc.identifier.issn1473-7140 (Linking)en_GB
dc.identifier.pmid20942635en_GB
dc.identifier.doi10.1586/era.10.148en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207899-
dc.description.abstractThe current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.en_GB
dc.language.isoengen_GB
dc.subject.meshAntineoplastic Agents/*therapeutic useen_GB
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols/therapeutic useen_GB
dc.subject.meshDeoxycytidine/*analogs & derivatives/therapeutic useen_GB
dc.subject.mesh*Drug Resistance, Neoplasmen_GB
dc.subject.meshFluorouracil/*analogs & derivatives/therapeutic useen_GB
dc.subject.meshHumansen_GB
dc.subject.meshNeoplasm Metastasisen_GB
dc.subject.meshPancreatic Neoplasms/*drug therapy/genetics/pathology/radiotherapyen_GB
dc.subject.meshProtein Kinase Inhibitors/therapeutic useen_GB
dc.subject.meshQuinazolines/*therapeutic useen_GB
dc.subject.meshReceptor, Epidermal Growth Factor/antagonists & inhibitorsen_GB
dc.subject.meshTreatment Outcomeen_GB
dc.subject.meshTumor Microenvironmenten_GB
dc.titleChallenges of drug resistance in the management of pancreatic cancer.en_GB
dc.contributor.departmentAdelaide and Meath Hospital incorporating The National Children's Hospital,, Tallaght, Dublin 24, Ireland. sheikh.rizwan68@gmail.comen_GB
dc.identifier.journalExpert review of anticancer therapyen_GB
dc.description.provinceLeinster-

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