TY - JOUR
T1 - Challenges and future directions in therapeutics for pancreatic ductal adenocarcinoma
AU - Al Haddad, Amal H.I.
AU - Adrian, Thomas E.
N1 - Funding Information:
The authors are supported by the Terry Fox Cancer Research Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2014 Informa UK, Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. The 5-year survival of < 5% has not changed in decades. In contrast to other major cancers, the incidence of PDAC is increasing.Areas covered: The aims of this paper are first to analyze why PDAC is so difficult to treat and, second, to suggest future directions for PDAC therapeutics. The authors provide an article that is based on a comprehensive search through MEDLINE and the clinicalTrials.gov website.Expert opinion: Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.
AB - Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. The 5-year survival of < 5% has not changed in decades. In contrast to other major cancers, the incidence of PDAC is increasing.Areas covered: The aims of this paper are first to analyze why PDAC is so difficult to treat and, second, to suggest future directions for PDAC therapeutics. The authors provide an article that is based on a comprehensive search through MEDLINE and the clinicalTrials.gov website.Expert opinion: Progress has been made recently. Notably, FOLFIRINOX or nab-paclitaxel plus gemcitabine provide survival benefit over gemcitabine alone, which was previously the mainstay of therapy for PDAC. Most of the current trials are testing combinations of repurposed drugs rather than addressing key targets in the PDAC pathogenesis. It is clear that to really make an impact on this disease, it will be necessary to address three different problems with targeted therapeutics. First, it is important to eradicate PDAC stem cells that result in recurrence. Second, it is important to reduce the peritumoral stroma that provides the tumors with growth support and provides a barrier to access of therapeutic agents. Finally, it is important to address the marked cachexia and metabolic derangement that contribute to morbidity and mortality and further complicate therapeutic intervention.
KW - Cachexia
KW - Cancer stem cells
KW - Pancreatic cancer
KW - Pancreatic ductal adenocarcinoma
KW - Therapy
KW - Tumor microenvironment
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U2 - 10.1517/13543784.2014.933206
DO - 10.1517/13543784.2014.933206
M3 - Review article
C2 - 25078674
AN - SCOPUS:84911469438
SN - 1354-3784
VL - 23
SP - 1499
EP - 1515
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 11
ER -