Challenges of drug resistance in the management of pancreatic cancer.
Sheikh, Rizwan Walsh, Naomi Clynes, Martin O'Connor, Robert McDermott, Ray
Sheikh, Rizwan
Walsh, Naomi
Clynes, Martin
O'Connor, Robert
McDermott, Ray
Advisors
Editors
Other Contributors
Date
2012-02-01T10:49:31Z
Date Submitted
Keywords
Other Subjects
Subject 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
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
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
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
ISSN
1744-8328 (Electronic)
1473-7140 (Linking)
1473-7140 (Linking)
eISSN
ISBN
DOI
10.1586/era.10.148
PMID
20942635