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Targeting KRAS in pancreatic adenocarcinoma: Progress in demystifying the holy grail

Ahmed Elhariri1, Ahmed Alhaj2, Daniel Ahn3

  • 1Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Florida, Mayo Clinic Cancer Center, Jacksonville, FL 32224, United States.

World Journal of Clinical Oncology
|September 13, 2023
PubMed

Insights

Pancreatic cancer (PC) survival is poor, largely due to the common Kirsten rat sarcoma virus (KRAS) mutation. This review explores challenges and promising trials targeting the previously "undruggable" KRAS pathway in PC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Pancreatic cancer (PC) has a dismal 5-year survival rate of approximately 11.5%.
  • The Kirsten rat sarcoma virus (KRAS) mutation is present in 90%-95% of PC patients and drives cancer progression.
  • KRAS has historically been considered
  • undruggable
  • due to challenges in developing targeted therapies.

Purpose of the Study:

  • To summarize current efforts to target the KRAS pathway in pancreatic cancer.
  • To discuss the challenges associated with KRAS-targeted therapy.
  • To highlight promising clinical trials for KRAS-mutated PC.

Main Methods:

  • Review of scientific literature on KRAS mutations in pancreatic cancer.
  • Analysis of therapeutic strategies targeting the KRAS pathway.
  • Examination of ongoing and completed clinical trials.

Main Results:

  • Despite extensive research, effective KRAS-targeted therapies for PC remain limited.
  • Significant challenges exist in drug development for KRAS-mutated cancers.
  • Several promising clinical trials are investigating novel approaches to target KRAS.

Conclusions:

  • Targeting the KRAS pathway is crucial for improving pancreatic cancer outcomes.
  • Overcoming the
  • undruggable
  • nature of KRAS requires innovative therapeutic strategies.
  • Ongoing clinical trials offer hope for more effective treatments for patients with KRAS-mutated PC.
Keywords:
Clustered regularly interspaced short palindromic repeatsDrug resistanceKirsten rat sarcoma virusNext generation sequencingPancreatic cancerTargeted therapy

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