Overcoming diagnostic issues in precision treatment of pancreatic cancer

ABSTRACT

Introduction: With high-throughput DNA analysis with next-generation sequencing (NGS), a new area of comprehensive molecular diagnostics is entering clinic. The profile of biomarkers (mutations and other abnormalities) may lay the foundation for precision treatment. Pancreatic ductal adenocarcinoma (PDAC) represents a challenge with its many aberrations spread over all pathways. Furthermore, suitable samples for molecular diagnostics are difficult to obtain, both for tissue-based (biopsy, cytology) and blood-based (cell-free DNA and circulating tumor cells [CTC]) assays.

Areas covered: Biomarkers, material, methods, and management of biomarkers for PDAC in precision treatment. Biomarkers refer multiple biomarkers at the same time. Material refers to the different biological sources including blood-based approaches with CTCs. Methods cover the analysis techniques such as NGS and RNA sequencing. Management comprises the handling of NGS and data analysis, as well as the need for clinically applicable, evidence-based recommendations.

Expert commentary: Outstanding problems are the procurement of samples suitable for multiplex biomarker analysis such as NGS. This may be overcome by single-cell sequencing. The final challenge, common to all approaches beyond a limited panel of genes, will be the holistic, evidence-based analysis of NGS data for making clinically relevant treatment recommendations. Outcome studies including cost-effectiveness are pivotal prior to reimbursement.

KEYWORDS:

• Artificial intelligence
• biomarker
• dataome
• next-generation sequencing
• oncology treatment decision support
• pancreatic cancer
• precision medicine

Acknowledgments

The work of the Pancreatic Cancer Research group (PaCaRes) at Karolinska Institutet, especially regarding precision medicine/PCM (PePaCaKa), has been supported over the years by grants from the Swedish Cancer Society (Cancerfonden), the Cancer Research Funds of Radiumhemmet (RaHFo), the Kamprad Family Foundation and an EU FP7 consortium CanDo for establishing CTC diagnostics in pancreatic cancer. Their generous support is acknowledged with deep gratitude. We also thank our patients, unnamed as they are, who never give up faith in our efforts.

Declaration of Interest

M Löhr has received honoraria from Centogene AG, a company specialized in molecular diagnostics. He is an external consultant to Molecular Health GmbH, the developer of MH Guide, a software for the analysis of NGS data. Unrelated to the subject of this article, M Löhr received honoraria for lecturing for Abbott, Mylan, Nordmark. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.