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New Horizons in the Treatment of Metastatic Pancreatic Cancer: A Review of the Key Biology Features and the Most Recent Advances to Treat Metastatic Pancreatic Cancer

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Abstract

Only a limited number of therapeutic strategies are available for patients diagnosed with pancreatic adenocarcinoma, and disease recurrence and mortality are consequently high. For metastatic disease, two combinations are approved in the first line setting: a triplet with 5-fluoruracil, irinotecan, and oxaliplatin, and the combination of gemcitabine and nab-paclitaxel. In patients who have progressed on gemcitabine, a new nanoliposomal formulation of irinotecan has recently been approved. While these treatments have demonstrated some efficacy, there has been little increase in survival rates for metastatic pancreatic cancer patients. Consequently, there is an urgent need for research and development of new treatments. As there is now a deeper understanding of pancreatic cancer biology, new drugs targeting altered pathways are under research, including agents that target TGF-β, IGF, or NOTCH. Furthermore, taking into account the role of the tumor stroma in this disease, some stroma-targeting drugs are being developed, including PEGPH20, a pegylated recombinant human hyaluronidase. In the immunotherapy field, although checkpoint inhibitors have failed to demonstrate benefit as monotherapies, combinations with other drugs are being investigated, with promising preliminary results. Other strategies under research are targeting tumor metabolism or DNA repair deficiency.

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Authors and Affiliations

  1. Vall d’Hebron Institute of Oncology and Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    Helena Verdaguer, Alvaro Arroyo & Teresa Macarulla

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  1. Helena Verdaguer
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  2. Alvaro Arroyo
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  3. Teresa Macarulla
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Correspondence to Helena Verdaguer.

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No external funding was used in the preparation of this manuscript.

Conflict of Interest

Teresa Macarulla has received research grants from Astrazeneca and Celgene, honoraria from Genzyme, Sanofi, Shire, Tesaro, Celgene, Roche, Baxalta and QED Therapeutic, and travel grants from Merck, H3 Biomedicine, Bayer and Sanofi. Helena Verdaguer has received honoraria from Celgene and Ipsen, and travel grants from Amgen, Celgene and Ipsen. Alvaro Arroyo declares that he does not have any conflicts of interest that might be relevant to the contents of this manuscript.

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Verdaguer, H., Arroyo, A. & Macarulla, T. New Horizons in the Treatment of Metastatic Pancreatic Cancer: A Review of the Key Biology Features and the Most Recent Advances to Treat Metastatic Pancreatic Cancer. Targ Oncol 13, 691–704 (2018). https://doi.org/10.1007/s11523-018-0609-7

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