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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 &gt;90% of all PDAC\u2019s; 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.<\/jats:p>","DOI":"10.3390\/curroncol31090385","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T02:25:49Z","timestamp":1725416749000},"page":"5206-5223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Systemic Therapy for Metastatic Pancreatic Cancer\u2014Current Landscape and Future Directions"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-3527","authenticated-orcid":false,"given":"Daniel","family":"Netto","sequence":"first","affiliation":[{"name":"The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Frizziero","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Foy","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-3678","authenticated-orcid":false,"given":"Mair\u00e9ad G.","family":"McNamara","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Backen","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Hubner","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"},{"name":"Division of Cancer Sciences, University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA A Cancer J. 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