A special subtype: Revealing the potential intervention and great value of KRAS wildtype pancreatic cancer

Biochim Biophys Acta Rev Cancer. 2022 Jul;1877(4):188751. doi: 10.1016/j.bbcan.2022.188751. Epub 2022 Jun 19.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the predominant form of pancreatic cancer and has devastating consequences on affected families and society. Its dismal prognosis is attributed to poor specificity of symptoms during early stages. It is widely believed that PDAC patients with the wildtype (WT) KRAS gene benefit more from currently available treatments than those with KRAS mutations. The oncogenic genetic changes alternations generally found in KRAS wildtype PDAC are related to either the KRAS pathway or microsatellite instability/mismatch repair deficiency (MSI/dMMR), which enable the application of tailored treatments based on each patient's genetic characteristics. This review focuses on targeted therapies against alternative tumour mechanisms in KRAS WT PDAC.

Keywords: KRAS; MSI; dMMR; kinase fusion; pancreatic cancer; precision medicine.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / pathology
  • Humans
  • Mutation
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)