Current Oncology (Sep 2024)

Systemic Therapy for Metastatic Pancreatic Cancer—Current Landscape and Future Directions

  • Daniel Netto,
  • Melissa Frizziero,
  • Victoria Foy,
  • Mairéad G. McNamara,
  • Alison Backen,
  • Richard A. Hubner

DOI
https://doi.org/10.3390/curroncol31090385
Journal volume & issue
Vol. 31, no. 9
pp. 5206 – 5223

Abstract

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Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-associated mortality, with a rising global incidence. A paucity of strong predictive risk factors mean screening programmes are difficult to implement. Historically, a lack of identifiable and actionable driver mutations, coupled with a relatively immunosuppressed tumour microenvironment, has led to a reliance on cytotoxic chemotherapy. The NAPOLI-3 trial has reported data supporting consideration of NALIRIFOX as a new first-line standard of care. Kirsten Rat Sarcoma Virus (KRAS) G12D mutations are present in >90% of all PDAC’s; exciting breakthroughs in small molecule inhibitors targeting KRAS G12D may open new modalities of treatment, and therapies targeting multiple KRAS mutations are also in early clinical trials. Although immunotherapy strategies to date have been disappointing, combination with chemotherapy and/or small molecule inhibitors hold promise and warrant further exploration.

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