Clinical update on K-Ras targeted therapy in gastrointestinal cancers

Shubham Pant, Joleen Hubbard, Erika Martinelli, Tanios Bekaii-Saab

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

KRAS mutations are common in pancreatic and colorectal cancers and are associated with lack of response to anti-epidermal growth factor receptor therapy. Ras is an established therapeutic target that has long eluded efforts to develop specific inhibitors, while targeting downstream signaling pathways has proven largely ineffective, highlighting a need for rational combination strategies to overcome resistance. Recently, renewed interest in directly targeting Ras has led to the development of several small-molecule inhibitors that bind directly to K-Ras or its effector proteins, downregulation of K-Ras expression using therapeutic antisense oligonucleotides or siRNAs, and targeting scaffold proteins such as kinase suppressor of Ras. Indirect approaches to inhibiting K-Ras include combining inhibitors of the mitogen-activated protein kinase pathway with novel targeted agents. Immunotherapy in early studies has also shown clinical promise. This review summarizes the current evidence for each of these approaches.

Original languageEnglish (US)
Pages (from-to)78-91
Number of pages14
JournalCritical Reviews in Oncology/Hematology
Volume130
DOIs
StatePublished - Oct 2018

Keywords

  • Colorectal cancer
  • Gastrointestinal cancer
  • K-Ras inhibitor
  • Pancreatic cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

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