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. 2014 Sep;19(9):937-50.
doi: 10.1634/theoncologist.2012-0131. Epub 2014 Aug 12.

Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

Free PMC article

Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

Joanne W Chiu et al. Oncologist. .
Free PMC article


The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance.

Keywords: Advanced pancreatic cancer; Biological therapy; Gemcitabine; Targeted therapy.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.


Figure 1.
Figure 1.
Major signaling pathways and potential actionable targets in advanced pancreatic cancer. Red lines and text indicate Food and Drug Administration-approved agents. Blue lines and text indicate agents that showed negative results in previous clinical trials. Olive green lines and text indicate agents in clinical trials. Abbreviations: EGFR, epidermal growth factor receptor; ERK, extracellular signal-related kinase; FTase, farnesyltransferase; FTI, farnesyltransferase inhibitor; GGTase I, geranylgeranyltransferase I; HER, human epidermal growth factor receptor; IGF-1R, insulin-like growth factor 1 receptor; MEK, mitogen-activated protein kinase/ERK kinase; MMP, matrix metalloproteinases; MMPI, MMP inhibitor; mTOR, mammalian target of rapamycin; PARP, poly (ADP-ribose) polymerase; PDGFR, platelet-derived growth factor receptor; PI3K, phosphoinositide 3-kinase; PSCA, prostate stem cell antigen; PTC, patched-1 receptor; PTEN, phosphatase and tensin homolog deleted on chromosome ten; SHH, sonic hedgehog; SMO, smoothened; SPARC, secreted protein acidic and rich in cysteine; TGF-β, transforming growth factor β; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.

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