Two Open Access reviews

1) Cancer Stem Cells in Pancreatic Cancer by Qi Bao and 6 co-authors, including Karl-Walter Jauch and Christiane J Bruns, Cancers 2010(Aug 19); 2(3): 1629-41. [Full text PDF][Scribd entry][Part of the Special Issue Pancreatic Cancer]. Abstract:

Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

2) The Emerging Role of the Phosphatidylinositol 3-Kinase/ Akt/Mammalian Target of Rapamycin Signaling Network in Cancer Stem Cell Biology by Alberto M Martelli and 4 co-authors, including James A McCubrey, Cancers 2010(Aug 18); 2(3): 1576-96. [Part of the Special Issue Cancer Stem Cells].

Comment: Review #2 is the first paper that has been published in the special issue on Cancer Stem Cells. As of August 20, 17 more contributions to this special issue are planned. Review #1, although about CSCs, is a contribution to a separate special issue on Pancreatic Cancer.

Review of current knowledge on pancreatic CSC

Role of cancer stem cells in pancreatic ductal adenocarcinoma by Gregory Sergeant, Hugo Vankelecom, Lies Gremeaux and Baki Topal, Nat Rev Clin Oncol 2009(Aug 18) [Epub ahead of print]. PubMed Abstract:

As our understanding of pancreatic cancer evolves, evidence is growing to support a role for cancer stem cells in this devastating disease. Cancer stem cells constitute a distinct subpopulation in the tumor and are considered to drive both tumorigenesis and metastasis; these cells are thought to be highly resistant to standard treatment modalities. Here we review the current knowledge on pancreatic cancer stem cells and the implementation of cancer stem cell markers as prognostic or predictive biomarkers. We also discuss prospects for the use of cancer stem cells as targets for future therapeutic regimens in pancreatic cancer.

[Found via CSC-related articles bookmarked in Connotea].

Combined treatment to eliminate CSC in pancreatic cancer

Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer by Maria-Theresa Mueller and 13 co-authors, including Christopher Heeschen, Gastroenterology 2009(Jun 4). PubMed Abstract:

BACKGROUND & AIMS:: Pancreatic cancers contain exclusively tumorigenic cancer stem cells (CSC), which are highly resistant to chemotherapy, resulting in a relative increase in CSC numbers during gemcitabine treatment. Signaling through sonic hedgehog and mTOR, respectively, may be essential for CSC self-renewal and could represent putative targets for novel treatment modalities. METHODS:: We used in vitro and in vivo models of pancreatic cancer to examine the effects of a sonic hedgehog inhibition (cyclopamine / CUR199691) and mTOR blockade (rapamycin) on the tumorigenic CSC population. RESULTS:: Surprisingly, neither cyclopamine nor rapamycin alone or as supplements to chemotherapy were capable of effectively diminishing the CSC pool. Only the combined inhibition of both pathways together with chemotherapy reduced the number of CSC to virtually undetectable levels in vitro and in vivo. Most importantly, in vivo administration of this triple combination in mice with established patient-derived pancreatic tumors was reasonably tolerated and translated into significantly prolonged long-term survival. CONCLUSIONS:: The combined blockade of sonic hedgehog and mTOR signaling together with standard chemotherapy is capable of eliminating pancreatic CSC. Further preclinical investigation of this promising approach may lead to the development of a novel therapeutic strategy to improve the devastating prognosis of patients with pancreatic cancer.

[Thanks to Alexey Bersenev].

Articles related to pancreatic cancer

Two articles on research related to pancreatic cancer have been published recently. They are:

1) Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer. M Mimeault and S K Batra, Gut 2008(Oct); 57(10): 1456-68. The last two sentences of the Abstract:

The combination of drugs that target the oncogenic elements in pancreatic cancer stem/progenitor cells and their microenvironment, with the conventional chemotherapeutic regimens, could represent promising therapeutic strategies. These novel targeted therapies should lead to the development of more effective treatments of locally advanced and metastatic pancreatic cancers, which remain incurable with current therapies.

At present, only the Abstract is freely-accessible. The publisher (BMJ Publishing Group) makes all archive content older than 12 months freely available to registered users. See: BMJ Journals information centre. See also the SHERPA/RoMEO summary of copyright policies for Gut.

2) An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer. G Feldmann and 13 co-authors, Mol Cancer Ther 2008(Sep); 7(9): 2725-35. The last sentence of the Abstract:

Pharmacologic blockade of aberrant Hedgehog signaling might prove to be an effective therapeutic strategy for inhibition of systemic metastases in pancreatic cancer, likely through targeting subsets of cancer cells with tumor-initiating ("cancer stem cell") properties.

At present, only the Abstract is freely-accessible. The publisher (American Association for Cancer Research) makes all articles available free 12 months after the date of initial publication. See: Access to AACR Publications. See also the SHERPA/RoMEO summary of copyright policies for AACR journals.