Personalised therapy for Pancreatic Cancer: Challenges and Opportunities

William Greenhalf, Eithne Costello, Paula Ghaneh, Thomas Hanna


Pancreatic Ductal Adenocarcinoma (PDAC) has one of the lowest 5-year survival rates of all cancers. Early metastatic spread and failure of standard chemotherapeutics both contribute to this statistic. Over the last decade many other cancer types have benefited from the targeted therapy revolution in which signalling networks found to be altered in cancer cells are specifically targeted. Despite an ever-growing understanding of the mutation profiles in PDAC, the vast majority of these approaches have failed for this form of malignancy. Chemotherapy, which simply targets dividing cells, remains the most effective available treatment option alongside surgery.  Although targeting a broad range of tyrosine kinase receptors with erlotinib has been shown to offer a modest improvement in the 5-year survival when combined with the pyrimidine-based chemotherapeutic gemcitabine; this suggests that targeted approaches may be of benefit in at least some patients.  PDAC is characterised by a long genomic tail of potentially actionable mutations but each appearing in only a small number of patients, making it difficult to show a survival benefit of a targeted therapy in an unselected group of patients. Identifying specific subpopulations based on molecular characterisation of the tumour is particularly difficult in PDAC because of problems in biospecimen acquisition; only a small proportion of patients undergo surgery and the organ is difficult to biopsy due to its location. Furthermore, PDAC is characterised by cellular heterogeneity within primary tumours and their metastases, meaning that targeted therapies may have only a transient effect, killing dominant cellular populations but leaving behind potentially even more aggressive forms of cancer cells that have unidentified (and so unexploited) molecular targets. In this review, consideration is given to overcoming the barriers of personalised medicine specific to PDAC with the aim of improving the 5-year survival rates


PDAC; targeted therapy; chemotherapy; circulating tumour cells; next generation sequencing;

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