Review Article | Published:

Pancreatic cancer: from state-of-the-art treatments to promising novel therapies

Nature Reviews Clinical Oncology volume 12, pages 319334 (2015) | Download Citation

Abstract

Pancreatic cancer is expected to be the second deadliest malignancy in the USA by 2020. The survival rates for patients with other gastrointestinal malignancies have increased consistently during the past 30 years; unfortunately, however, the outcomes of patients with pancreatic cancer have not changed significantly. Although surgery remains the only curative treatment for pancreatic cancer, therapeutic strategies based on initial resection have not substantially improved the survival of patients with resectable disease over the past 25 years; presently, more than 80% of patients suffer disease relapse after resection. Preclinical evidence that pancreatic cancer is a systemic disease suggests a possible benefit for early administration of systemic therapy in these patients. In locally advanced disease, the role of chemoradiotherapy is increasingly being questioned, particularly considering the results of the LAP-07 trial. Novel biomarkers are clearly needed to identify subsets of patients likely to benefit from chemoradiotherapy. In the metastatic setting, FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin), and nab-paclitaxel plus gemcitabine have yielded only modest improvements in survival. Thus, new treatments are urgently needed for patients with pancreatic cancer. Herein, we review the state-of-the-art of pancreatic cancer treatment, and the upcoming novel therapeutics that hold promise in this disease are also discussed.

Key points

  • Patient survival after resection of pancreatic ductal adenocarcinoma (PDAC) remains poor and more-effective adjuvant treatments are desperately needed; new strategies under investigation include targeting the tumour stroma and cancer stem cell compartment

  • Neoadjuvant therapy might improve the delivery of chemotherapy and radiation, and can enable early treatment of metastatic PDAC

  • The role of chemoradiotherapy in the treatment of locally advanced PDAC is highly controversial; SMAD4 (DPC4) might represent a biomarker that identifies a subset of patients who could benefit from radiation added to systemic chemotherapy

  • Modest success has been achieved with FOLFIRINOX, and with novel cytotoxic agents (nab-paclitaxel and MM-398, for example) in the metastatic setting

  • Immunotherapy (with the GVAX vaccine) has produced promising results in highly selected patients

  • Preclinical data suggest that therapies that remodel the stroma or increase programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression might unveil activity of immune-checkpoint inhibitors

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Acknowledgements

The work of I.G.-L. is supported by funding from the NIH National Cancer Institute (Grant P30CA042014-23 to the Huntsman Cancer Institute). The authors thank Joan Aaron for her language editing of this article on a voluntary basis and Claire Gartrell of the Huntsman Cancer Institute, Salt Lake City, UT, USA, for editing Figure 1 before submission.

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Affiliations

  1. Department of Internal Medicine, Division of Oncology, and Center for Investigational Therapeutics, Huntsman Cancer Institute, University of Utah School of Medicine, University of Utah, Suite 2100, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.

    • Ignacio Garrido-Laguna
  2. Gastrointestinal Cancer Clinical Research Unit, Clinical Research Program, Spanish National Cancer Research Centre (CNIO), Calle de Melchor Fernández Almagro 3, 28029 Madrid, Spain.

    • Manuel Hidalgo

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Contributions

Both authors made substantial contributions to all stages of the preparation of the manuscript for submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ignacio Garrido-Laguna.

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DOI

https://doi.org/10.1038/nrclinonc.2015.53

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