Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 40, Issue 24, Pages 2693-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1200/JCO.21.02514
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Funding
- Pancreatic Cancer Research Fund
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Managing pancreatic ductal adenocarcinoma (PDAC) has been a challenge, but a deeper understanding of its biology has provided guidance for precision treatment. Specific PDAC subgroups and KRAS wild-type PDAC can be targeted for treatment, and genomic- and transcriptomic-based classifiers can be used in clinical trials.
The management of pancreatic ductal adenocarcinoma (PDAC) has posed a considerable challenge for decades, with incidence and mortality rates almost mirroring each other. Despite this, a deeper understanding of the complex biology inherent to PDAC has provided a roadmap for a more precise approach to treatment. PDAC deficient in homologous recombination repair and mismatch repair is a subgroup that should be identified in the clinic for a targeted approach. In addition, KRAS wild-type PDAC, occurring in approximately 10% of patients, is enriched in highly actionable alterations including fusions, underscoring the importance of integrative germline and somatic sequencing. Comprehensive sequencing efforts over the past decade have documented genomic- and transcriptomic-based classifiers, with the latter emerging as two main subtypes: the classical and basal-like, which are now being evaluated in clinical trials. Together with promising, innovative strategies to target KRAS mutations and their pleotropic effects, a new era of precision medicine in PDAC is on the horizon.
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